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Mechanisms of vaccine adjuvanticity at mucosal surfaces

Published online by Cambridge University Press:  28 February 2007

Dennis L. Foss
Affiliation:
Department of Veterinary PathoBiology, University of Minnesota St. Paul, MN 55108, USA
Michael P. Murtaugh*
Affiliation:
Department of Veterinary PathoBiology, University of Minnesota St. Paul, MN 55108, USA

Abstract

The vast majority of pathogens invade via mucosal surfaces, including those of the intestine. Vaccination directly on these surfaces may induce local protective immunity and prevent infection and disease. Although vaccine delivery to the gut mucosa is fraught with obstacles, immunization can be enhanced using adjuvants with properties specific to intestinal immunity. In this review, we present three general mechanisms of vaccine adjuvant function as originally described by Freund, and we discuss these principles with respect to intestinal adjuvants in general and to the prototypical mucosal adjuvant, cholera toxin. The key property of intestinal adjuvants is to induce an immunogenic context for the presentation of the vaccine antigen. The success of oral vaccine adjuvants is determined by their ability to induce a controlled inflammatory response in the gut-associated lymphoid tissues, characterized by the expression of various costimulatory molecules and cytokines. An understanding of the specific molecular mechanisms of adjuvanticity in the gut will allow the rational development of safe and effective oral vaccines.

Type
Research Article
Copyright
Copyright © CAB International 2000

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References

Agren, LC, Ekman, L, Lowenadler, B and Lycke, NY (1997). Genetically engineered nontoxic vaccine adjuvant that combines B cell targeting with immunomodulation by cholera toxin A1 subunit. Journal of Immunology 158: 39363946.CrossRefGoogle ScholarPubMed
Ahlers, JD, Dunlop, N, Alling, DW, Nara, PL and Berzofsky, JA (1997). Cytokine-in-adjuvant steering of the immune response phenotype to HIV-1 vaccine constructs— granulocyte-macrophage colony-stimulating factor and TNF-α synergize with IL-12 to enhance induction of cytotoxic T lymphocytes. Journal of Immunology 158: 39473958.Google Scholar
Al-Sabbagh, A, Nelson, PA, Akselband, Y, Sobel, RA and Weiner, HL (1996). Antigen-driven peripheral immune tolerance: suppression of experimental autoimmmune encephalomyelitis and collagen-induced arthritis by aerosol administration of myelin basic protein or type-II collagen. Cellular Immunology 171: 111119.CrossRefGoogle ScholarPubMed
Bailey, M, Miller, BG, Telemo, E, Stokes, CR and Bourne, FJ (1993). Specific immunological unresponsiveness following active primary responses to proteins in the weaning diet of piglets. International Archives of Allergy and Immunology 101: 266271.CrossRefGoogle ScholarPubMed
Bailey, M, Miller, BG, Telemo, E, Stokes, CR and Bourne, FJ (1994). Altered immune response to proteins fed after neonatal exposure of piglets to the antigen. International Archives of Allergy and Immunology 103: 183187.Google Scholar
Bergquist, C, Johansson, EL, Lagergard, T, Holmgren, J and Rudin, A (1997). Intranasal vaccination of humans with recombinant cholera toxin B subunit induces systemic and local antibody responses in the upper respiratory tract and the vagina. Infection and Immunity 65: 26762684.Google Scholar
Bern, C, Martines, J, de Zoysa, I and Glass, RI (1992). The magnitude of the global problem of diarrhoeal disease: a ten year update. Bulletin of the World Health Organization 70: 705714.Google ScholarPubMed
Blecha, F, Reddy, DN, Chitko-McKown, CG, Mcvey, DS, Chengappa, MM, Goodband, RD and Nelssen, JL (1995). Influence of recombinant bovine interleukin-1 beta and interleukin-2 in pigs vaccinated and challenged with Streptococcus suis. Veterinary Immunology and Immunopathology 44: 329346.Google Scholar
Boehm, U, Klamp, T, Groot, M and Howard, JC (1997). Cellular responses to interferon-gamma. Annual Review of Immunology 15: 749795.CrossRefGoogle ScholarPubMed
Bost, KL and Clements, JD (1995). In vivo induction of interleukin-12 mRNA expression after oral immunization with Salmonella dublin or the B subunit of Escherichia coli heat-labile enterotoxin. Infection and Immunity 63: 10761083.CrossRefGoogle ScholarPubMed
Braun, MC, He, JP, Wu, CY and Kelsall, BL (1999). Cholera toxin suppresses interleukin (IL)-12 production and IL-12 receptor beta 1 and beta 2 chain expression. Journal of Experimental Medicine 189: 541552.CrossRefGoogle Scholar
Bromander, A, Holmgren, J and Locke, N (1991). Cholera toxin stimulates IL-1 production and enhances antigen presentation by macrophages in vitro. Journal of Immunology 146: 29082914.Google Scholar
Buckley, NE, Su, Y, Milstien, S and Spiegal, S (1995). The role of calcium influx in cellular proliferation induced by interaction of endogenous ganglioside GM1 with the B subunit of cholera toxin. Biochimica et Biophysica Acta 1256: 275283.Google Scholar
Bush, K, Day, NK, Kraus, LA, Good, RA and Bradley, WG (1994). Molecular cloning of feline interleukin 12 p35 reveals the conservation of leucine-zipper motifs present in human and murine IL-12 p35. Molecular Immunology 31: 13731374.Google Scholar
Cameron, LA, Taha, RA, Tsicopoulos, A, Kurimoto, M, Olivenstein, R, Wallaert, B, Minshall, EM and Hamid, QA (1999). Airway epithelium expresses interleukin-18. European Respiratory Journal 14: 553559.CrossRefGoogle ScholarPubMed
Centers for Disease Control and Prevention (1997). Multidrug-resistant Salmonella serotype typhimurium—United States, 1996. Journal of the American Medical Association 277: 15131516.CrossRefGoogle Scholar
Cesano, A, Visonneau, S, Clark, SC and Santoli, D (1993). Cellular and molecular mechanisms of activation of MHC nonrestricted cytotoxic cells by IL-12. Journal of Immunology 151: 29432957.Google Scholar
Challacombe, SJ and Tomasi, TB Jr (1980). Systemic tolerance and secretory immunity after oral immunization. Journal of Experimental Medicine 152: 14591472.CrossRefGoogle ScholarPubMed
Challacombe, SJ, Rahman, D and Ohagan, DT (1997). Salivary, gut, vaginal and nasal antibody responses after oral immunization with biodegradable microparticles. Vaccine 15: 169175.Google Scholar
Chan, SH, Kobayashi, M, Santoli, D, Perussia, B and Trinchieri, G (1992). Mechanisms of IFN-gamma induction by natural killer cell stimulatory factor (NKSF/IL-12). Role of transcription and mRNA stability in the synergistic interaction between NKSF and IL-2. Journal of Immunology 148: 9298.Google Scholar
Chandra, G, Cogswell, JP, Miller, LR, Godlevski, MM, Stinnett, SW, Noel, SL, Kadwell, SH, Kost, TA and Gray, JG (1995). Cyclic AMP signaling pathways are important in IL-1 beta transcriptional regulation. Journal of Immunology 155: 45354543.CrossRefGoogle ScholarPubMed
Chase, M (1946). Inhibition of experimental drug allergy by prior feeding of the sensitizing agent. Proceedings of the Society for Experimental Biology and Medicine 61: 257259.CrossRefGoogle ScholarPubMed
Chen, Y, Inobe, J, Marks, R, Gonnella, P, Kuchroo, VK and Weiner, HL (1995 a). Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature 376: 177180.Google Scholar
Chen, Y, Inobe, J and Weiner, HL (1995 b). Induction of oral tolerance to myelin basic protein in CD8-depleted mice: both CD4+ and CD8+ cells mediate active suppression. Journal of Immunology 155: 910916.CrossRefGoogle ScholarPubMed
Clemens, D, Sack, DA, Chakraborty, J, Rao, MR, Ahmed, F, Harris, JR, van Loon, FPL, Khan, MR, Yunis, M and Huda, S (1990). Field trial of oral cholera vaccines in Bangladesh: evaluation of anti-bacterial and anti-toxin breast-milk immunity in response to ingestion of the vaccine. Vaccine 8: 469472.CrossRefGoogle Scholar
Clemens, JD, Stanton, BF, Chakraborty, J, Sack, DA, Khan, MR, Huda, S, Ahmed, F, Harris, JR, Yunus, M, Khan, MU, Svennerholm, AM, Jertborn, M and Holmgren, J (1987). B subunit-whole cell and whole cell-only vaccines against cholera: studies on reactivity and immunogenicity. Journal of Infectious Diseases 155: 7985.Google Scholar
Cox, JC and Coulter, AR (1997). Adjuvants—a classification and review of their modes of action. Vaccine 15: 248256.CrossRefGoogle ScholarPubMed
Culshaw, RJ, Bancroft, GJ and Mcdonald, V (1997). Gut intraepithelial lymphocytes induce immunity against cryptosporidium infection through a mechanism involving gamma interferon production. Infection and Immunity 65: 30743079.Google Scholar
Curtsinger, JM, Schmidt, CS, Mondino, A, Lins, DC, Kedl, RM, Jenkins, MK and Mescher, MF (1999). Inflammatory cytokines provide a third signal for activation of naive CD4(+) and CD8(+) T cells. Journal of Immunology 162: 32563262.Google Scholar
D'Andrea, A, Aste Amezaga, M, Valiante, NM, Ma, X, Kubin, M and Trinchieri, G (1993). Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. Journal of Experimental Medicine 178: 10411048.CrossRefGoogle ScholarPubMed
De Aizpurua, HJ and Russell-Jones, GJ (1988). Oral vaccination. Identification of classes of proteins that provoke an immune response upon oral feeding. Journal of Experimental Medicine 167: 440451.Google Scholar
De Haan, L, Holtrop, M, Verweij, WR, Agsteribbe, E and Wilschut, J (1996 a). Mucosal immunogenicity of the Escherichia coli heat-labile enterotoxin: role of the A subunit. Vaccine 14: 260266.Google Scholar
De Haan, L, Verweij, WR, Feil, IK, Lijnema, TH, Hol, WGJ, Agsteribbe, E and Wilschut, J (1996 b). Mutants of the Escherichia coli heat-labile enterotoxin with reduced ADP-ribosylation activity or no activity retain the immunogenic properties of the native holotoxin. Infection and Immunity 64: 54135416.CrossRefGoogle ScholarPubMed
Dinarello, CA (1999). IL-18: a Th1-inducing, proinflammatory cytokine and new member of the IL-1 family. Journal of Allergy and Clinical Immunology 103: 1124.Google Scholar
Ding, L, Linsley, PS, Huang, LY, Germain, RN and Shevach, EM (1993). IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. Journal of Immunology 151: 12241234.CrossRefGoogle ScholarPubMed
Douce, G, Turcotte, C, Cropley, I, Roberts, M, Pizza, M, Domenghini, M, Rappuoli, R and Dougan, G (1995). Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants. Proceedings of the National Academy of Sciences of the United States of America 92: 16441648.CrossRefGoogle ScholarPubMed
Douce, G, Fontana, M, Pizza, M, Rappuoli, R and Dougan, G (1997). Intranasal immunogenicity and adjuvanticity of site-directed mutant derivatives of cholera toxin. Infection and Immunity 65: 28212828.CrossRefGoogle ScholarPubMed
Douce, G, Giannelli, V, Pizza, M, Lewis, D, Everest, P, Rappuoli, R and Dougan, G (1999). Genetically detoxified mutants of heat-labile toxin from Escherichia coli are able to act as oral adjuvants. Infection and Immunity 67: 44004406.Google Scholar
Dresser, DW (1961). Effectiveness of lipid and lipidophilic substances as adjuvants. Nature 191: 11691171.CrossRefGoogle ScholarPubMed
Duchmann, R, Kaiser, I, Hermann, E, Mayet, W, Ewe, K and Zumbuschenfelde, KHM (1995). Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clinical and Experimental Immunology 102: 448455.Google Scholar
Edelman, R (1997). Adjuvants for the future. In: Levine, MM, Woodrow, GC, Kaper, JB and Cobon, GS (eds) New Generation Vaccines. New York: Marcel Dekker, pp. 112.Google Scholar
Ehrhardt, RO, Ludviksson, BR, Gray, B, Neurath, M and Strober, W (1997). Induction and prevention of colonic inflammation in IL-2-deficient mice. Journal of Immunology 158: 566573.Google Scholar
Elhofy, A and Bost, KL (1999). Limited interleukin-18 response in Salmonella-infected murine macrophages and in Salmonella-infected mice. Infection and Immunity 67: 50215026.CrossRefGoogle ScholarPubMed
Ellem, KAO, Orourke, MGE, Johnson, GR, Parry, G, Misko, IS, Schmidt, CW, Parsons, PG, Burrows, SR, Cross, S, Fell, A, Li, CL, Bell, JR, Dubois, PJ, Moss, DJ, Good, MF, Kelso, A, Cohen, LK, Dranoff, G and Mulligan, RC (1997). A case report—immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy. Cancer Immunology and Immunotherapy 44: 1020.CrossRefGoogle Scholar
Elson, CO and Dertzbaugh, MT (1994). Mucosal adjuvants. In: Ogra, PA, Mestecky, J, Lamm, ME, Strober, W, McGhee, JR and Bienenstock, J (eds) Handbook of Mucosal Immunology. San Diego: Academic Press, pp. 391402.Google Scholar
Elson, CO and Ealding, W (1984). Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin. Journal of Immunology 132: 27362741.Google Scholar
Elson, CO, Holland, SP, Dertzbaugh, MT, Cuff, CF and Anderson, AO (1995). Morphologic and functional alterations of mucosal T cells by cholera toxin and its B subunit. Journal of Immunology 154: 10321040.Google Scholar
Fearon, DT and Locksley, RM (1996). The instructive role of innate immunity in the acquired immune response. Science 272: 5054.CrossRefGoogle ScholarPubMed
Foss, DL (1998). Mucosal Adjuvanticity of Cholera Toxin in Swine. PhD Thesis, University of Minnesota.Google Scholar
Foss, DL and Murtaugh, MP (1997). Molecular cloning and mRNA expression of porcine interleukin-12. Veterinary Immunology and Immunopathology 57: 121134.CrossRefGoogle ScholarPubMed
Foss, DL and Murtaugh, MP (1999). Mucosal immunogenicity and adjuvanticity of cholera toxin in swine. Vaccine 17: 788801.Google Scholar
Foss, DL, Moody, M, Murphy, KP Jr, Pazmany, C, Zilliox, MJ and Murtaugh, MP (1999 a). In vitro and in vivo bioactivity of single-chain interleukin-12. Scandinavian Journal of Immunology 50: 596604.Google Scholar
Foss, DL, Zilliox, MJ and Murtaugh, MP (1999 b). Differential regulation of macrophage interleukin-1 (IL-1), IL-12, and CD80-CD86 by two bacterial toxins. Infection and Immunity 67: 52755281.Google Scholar
Francis, ML, Okazaki, I, Moss, J, Kurosky, A, Pecanha, LMT and Mond, JJ (1995). cAMP-independent effects of cholera toxin on B cell activation. III. Cholera toxin A subunit-mediated ADP-ribosylation acts synergistically with ionomycin or IL-4 to induce B cell proliferation. Journal of Immunology 154: 49564964.CrossRefGoogle ScholarPubMed
Freund, J (1951). The effect of paraffin oil and mycobacteria on antibody formation and sensitization. American Journal of Clinical Pathology 21: 645656.Google Scholar
Freund, J, Casals, J and Hosmer, EP (1937). Sensitization and antibody formation after injection of tubercle bacilli and paraffin oil. Proceedings of the Society for Experimental Biology and Medicine 37: 509513.CrossRefGoogle Scholar
Freund, J, Casals-Ariet, J and Schaefer-Genghof, D (1940). The synergistic effect of paraffin-oil combined with heat-killed tubercule-bacilli. Journal of Immunology 38: 6779.Google Scholar
Friedman, A and Weiner, HL (1994). Induction of anergy or active suppression following oral tolerance is determined by antigen dosage. Proceedings of the National Academy of Sciences of the United States of America 91: 66886692.Google Scholar
Gardenas, L and Clements, JD (1992). Oral immunization using live attenuated Salmonella spp. as carriers of foreign antigen. Clinical and Microbiological Reviews 5: 328342.CrossRefGoogle Scholar
Garside, P and Mowat, AM (1997). Mechanisms of oral tolerance. Critical Reviews in Immunology 17: 119137.CrossRefGoogle ScholarPubMed
Gately, MK, Wilson, DE and Wong, HL (1986). Synergy between recombinant interleukin 2 (rIL-2) and IL 2-depleted lymphokine-containing supernatants in facilitating allogeneic human cytolytic T lymphocyte responses in vitro. Journal of Immunology 136: 12741282.Google Scholar
Ghayur, T, Banerjee, S, Hugunin, M, Butler, D, Herzog, L, Carter, A, Quintal, L, Sekut, L, Talanian, R, Paskind, M, Wong, W, Kamen, R, Tracey, D and Allen, H (1997). Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature 386: 619623.Google Scholar
Gregerson, DS, Obritsch, WF and Donoso, LA (1993). Oral tolerance in experimental autoimmune uveoretinitis. Distinct mechanisms of resistance are induced by low dose versus high dose feeding protocols. Journal of Immunology 151: 57515761.Google Scholar
Grohmann, U, Bianchi, R, Ayroldi, E, Belladonna, ML, Surace, D, Fioretti, MC and Puccetti, P (1997). A tumor-associated and self antigen peptide presented by dendritic cells may induce T cell anergy in vivo, but IL-12 can prevent or revert the anergic state. Journal of Immunology 158: 35933602.Google Scholar
Gu, Y, Kuida, K, Tsutsui, H, Ku, G, Hsiao, K, Fleming, MA, Hayashi, N, Higashino, K, Okamura, H, Nakanishi, K, Kurimoto, M, Tanimoto, T, Flavell, RA, Sato, V, Harding, MW, Livingston, DJ and Su, MSS (1997). Activation of interferon-gamma inducing factor mediated by interleukin-1-beta converting enzyme. Science 275: 206209.CrossRefGoogle Scholar
Gubler, U, Chua, AO, Schoenhaut, DS, Dwyer, CM, McComas, W, Motyka, R, Nabavi, N, Wolitzky, AG, Quinn, PM, Familletti, PC and Gately, MK (1991). Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor. Proceedings of the National Academy of Sciences of the United States of America 88: 41434147.CrossRefGoogle Scholar
Gyles, CL and Barnum, DA (1969). A heat-labile enterotoxin from strains of Escherichia coli enteropathogenic for pigs. Journal of Infectious Diseases 120: 419426.Google Scholar
Hajishengallis, G, Hollingshead, SK, Koga, T and Russell, MW (1995). Mucosal immunization with a bacterial protein antigen genetically coupled to cholera toxin A2/B subunits. Journal of Immunology 154: 43224332.Google Scholar
Hajishengallis, G, Michalek, SM and Russell, MW (1996). Persistence of serum and salivary antibody responses after oral immunization with a bacterial protein antigen genetically linked to the A2/B subunits of cholera toxin. Infection and Immunity 64: 665667.Google Scholar
Harokopakis, E, Hajishengallis, G, Greenway, TE, Russell, MW and Michalek, SM (1997). Mucosal immunogenicity of a recombinant Salmonella typhimurium—cloned heterologous antigen in the absence or presence of coexpressed cholera toxin A2 and B subunits. Infection and Immunity 65: 14451454.CrossRefGoogle ScholarPubMed
Heinzel, FP, Rerko, RM, Ling, P, Hakimi, J and Schoenhaut, DS (1994). Interleukin 12 is produced in vivo during endotoxemia and stimulates synthesis of gamma interferon. Infection and Immunity 62: 42444249.Google Scholar
Heinzel, FP, Hujer, AM, Ahmed, FN and Rerko, RM (1997). In vivo production and function of IL-12 p40 homodimers. Journal of Immunology 158: 43814388.CrossRefGoogle ScholarPubMed
Hsieh, CS, Macatonia, SE, Tripp, CS, Wolf, SF, O'Garra, A and Murphy, KM (1993). Development of Th1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 260: 547549.CrossRefGoogle ScholarPubMed
Hughes, HPA (1998). Cytokine adjuvants—lessons from the past—guidelines for the future. Veterinary Immunology and Immunopathology 63: 131138.CrossRefGoogle ScholarPubMed
Hunter, CA, Chizzonite, R and Remington, JS (1995). IL-1 beta is required for IL-12 to induce production of IFN-gamma by NK cells—a role for IL-1 beta in the T cell-independent mechanism of resistance against intracellular pathogens. Journal of Immunology 155: 43474354.Google Scholar
Jackson, RJ, Marinaro, M, VanCott, JL, Yamamoto, M, Okahashi, N, Fujihashi, K, Kiyono, H, Chatfield, SN and McGhee, JR (1996). Mucosal immunity—regulation by helper T cells and a novel method for detection. Journal of Biotechnology 44: 209216.Google Scholar
Jain, SL, Barone, KS, Flanagan, MP and Michael, JG (1996). Activation patterns of murine B cells after oral administration of an encapsulated soluble antigen. Vaccine 14: 4248.Google Scholar
Jenkins, MK, Chen, C, Jung, G, Mueller, DL and Schwartz, RH (1991). Inhibition of antigen-specific proliferation of type 1 murine T cell clones after stimulation with immobilized anti-CD3 monclonal antibody. Journal of Immunology 144: 1622.CrossRefGoogle Scholar
Jertborn, M, Svennerholm, AM and Holmgren, J (1986). Gut mucosal, salivary and serum antitoxic and antibacterial antibody responses in Swedes after oral immunization with B subunit-whole cell cholera vaccine. International Archives of Allergy and Applied Immunology 75: 3843.Google Scholar
Johnson, AG, Gaines, S and Landy, M (1956). Studies on the O antigen of Salmonella typhosa: V. Enhancement of antibody response to protein antigens by the purified lipopolysaccharide. Journal of Experimental Medicine 103: 225246.Google Scholar
Johnson, JG and Jenkins, MK (1994). Minireview: the role of anergy in peripheral T cell unresponsiveness. Life Sciences 55: 17671780.Google Scholar
Jones, BD, Ghori, N and Falkow, S (1994). Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches. Journal of Experimental Medicine 180: 1523.Google Scholar
Karasszon, D (1988). A Concise History of Veterinary Medicine. Budapest: Akademiai Kiado.Google Scholar
Kelly, SM, Bosecker, BA and Curtiss, R (1992). Characterization and protective properties of attenuated mutant of Salmonella cholerasuis. Infection and Immunity 60: 48814890.Google Scholar
Kensil, CR, Patel, U, Lennick, M and Marciani, D (1991). Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex. Journal of Immunology 146: 431437.CrossRefGoogle ScholarPubMed
Khoruts, A, Mondino, A, Pape, KA, Reiner, SL and Jenkins, MK (1998). A natural immunological adjuvant enhances T cell clonal expansion through a CD28-dependent, interleukin (IL)-2-independent mechanism. Journal of Experimental Medicine 187: 225236.Google Scholar
Kim, JJ, Ayyavoo, V, Bagarazzi, ML, Chattergoon, M, Boyer, JD, Wang, B and Weiner, BD (1997). Development of a multicomponent candidate vaccine for HIV-1. Vaccine 15: 879883.Google Scholar
Kim, YM, Kang, HS, Paik, SG, Pyun, KH, Anderson, KL, Torbett, BE and Choi, I (1999). Roles of IFN consensus sequence binding protein and PU.1 in regulating IL-18 gene expression. Journal of Immunology 163: 20002007.CrossRefGoogle ScholarPubMed
Kincycain, T and Bost, KL (1996). Increased susceptibility of mice to salmonella infection following in vivo treatment with the substance P antagonist, spantide II. Journal of Immunology 157: 255264.Google Scholar
Kincycain, T and Bost, KL (1997). Substance P-induced IL-12 production by murine macrophages. Journal of Immunology 158: 23342339.Google Scholar
Kincycain, T, Clements, JD and Bost, KL (1996). Endogenous and exogenous interleukin-12 augment the protective immune response in mice orally challenged with Salmonella dublin. Infection and Immunity 64: 14371440.CrossRefGoogle ScholarPubMed
Kjerrulf, M, Grdic, D, Ekman, L, Schon, K, Vajdy, M and Lycke, NY (1997). Interferon-gamma receptor-deficient mice exhibit impaired gut mucosal immune responses but intact oral tolerance. Immunology 92: 6068.Google Scholar
Klein, JR (1996). Whence the intestinal intraepithelial lymphocyte. Journal of Experimental Medicine 184: 12031206.Google Scholar
Kobayashi, M, Fitz, L, Ryan, M, Hewick, RM, Clark, SC, Chan, S, Loudon, R, Sherman, F, Perussia, B and Trinchieri, G (1989). Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. Journal of Experimental Medicine 170: 827845.Google Scholar
Kochnolte, F, Haag, F, Kastelein, R and Bazan, F (1996). Uncovered—the family relationship of a T-cell-membrane protein and bacterial toxins. Immunology Today 17: 402405.Google Scholar
Kohno, K, Kataoka, J, Ohtsuki, T, Suemoto, Y, Okamoto, I, Usui, M, Ikeda, M and Kurimoto, M (1997). IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. Journal of Immunology 158: 15411550.CrossRefGoogle Scholar
Kraehenbuhl, JP and Neutra, MR (1992). Molecular and cellular basis of immune protection of mucosal surfaces. Physiological Reviews 72: 853879.CrossRefGoogle ScholarPubMed
Krakauer, T (1996). Evidence for protein kinase C pathway in the response of human peripheral blood mononuclear cells to cholera toxin. Cellular Immunology 172: 224228.Google Scholar
Kubota, M, Miller, CJ, Imaoka, K, Kawabata, S, Fujihashi, K, McGhee, JR and Kiyono, H (1997). Oral immunization with simian immunodeficiency virus p55(gag) and cholera toxin elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates. Journal of Immunology 158: 53215329.Google Scholar
Kühn, R, Löhler, J, Rennick, D, Rajewsky, K and Müller, W (1993). Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75: 263274.Google Scholar
Lencer, WI, Delp, C, Neutra, MR and Madara, JL (1992). Mechanism of cholera toxin action on a polarized human intestinal epithelial cell line: role of vesicular traffic. Journal of Cell Biology 117: 11971209.Google Scholar
Lencer, WI, Constable, C, Moe, S, Jobling, MG, Webb, HM, Ruston, S, Madara, JL, Hirst, TR and Holmes, RK (1995). Targeting of cholera toxin and Escherichia coli heat labile toxin in polarized epithelia: role of COOH-terminal KDEL. Journal of Cell Biology 131: 951962.Google Scholar
Levine, MM and Lagos, R (1997). Vaccines and vaccination in historical perspective. In: Levine, MM, Woodrow, GC, Kaper, JB and Cobon, GS (eds) New Generation Vaccines. New York: Marcel Dekker, pp. 112.Google Scholar
Li, DF, Nelssen, JL, Reddy, PG, Blecha, F, Hancock, JD, Allee, GL, Goodband, RD and Klemm, RD (1990). Transient hypersensitivity to soybean meal in the early-weaned pig. Journal of Animal Science 68: 17901799.CrossRefGoogle ScholarPubMed
Li, DF, Nelssen, JL, Reddy, PG, Blecha, F, Klemm, R and Goodband, RD (1991). Interrelationship between hypersensitivity to soybean proteins and growth performance in early-weaned pigs. Journal of Animal Science 69: 40624069.Google Scholar
Lindblad, EB, Elhay, MJ, Silva, R, Appelberg, R and Andersen, P (1997). Adjuvant modulation of immune responses to tuberculosis subunit vaccines. Infection and Immunity 65: 623629.CrossRefGoogle ScholarPubMed
Lomotan, EA, Brown, KA, Speaker, TJ and Offita, PA (1997). Aqueous-based microcapsules are detected primarily in gut-associated dendritic cells after oral inoculation of mice. Vaccine 15: 19591962.Google Scholar
Lycke, NY (1993). Cholera toxin promotes B cell isotype switching by two different mechanisms: cAMP induction augments germ-line Ig H-chain RNA transcripts whereas membrane ganglioside GM1—receptor binding enhances later events in differentiation. Journal of Immunology 150: 48104821.CrossRefGoogle ScholarPubMed
Lycke, N and Holmgren, J (1986). Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens. Immunology 59: 301308.Google Scholar
Lycke, N and Strober, W (1989). Cholera toxin promotes B cell isotype differentiation. Journal of Immunology 142: 37813787.CrossRefGoogle ScholarPubMed
Lycke, N, Bromander, A, Ekman, L, Karlsson, U and Holmgren, J (1989 a). Cellular basis of immunomodulation by cholera toxin in vitro with possible association to the adjuvant function in vivo. Journal of Immunology 142: 2027.CrossRefGoogle Scholar
Lycke, N, Bromander, AK and Holmgren, J (1989 b). Role of local IgA antitoxin-producing cells for intestinal protection against cholera toxin challenge. International Archives of Allergy and Applied Immunology 88: 273279.Google Scholar
Lycke, N, Severinson, E and Strober, W (1990). Cholera toxin acts synergistically with IL-4 to promote IgG1 switch differentiation. Journal of Immunology 145: 33163324.Google Scholar
Lycke, N, Karlsson, U, Sjolander, A and Magnusson, KE (1991). The adjuvant action of cholera toxin is associated with an increased intestinal permeability for luminal antigens. Scandinavian Journal of Immunology 33: 691698.CrossRefGoogle ScholarPubMed
Lycke, N, Tsuji, T and Holmgren, J (1992). The adjuvant effect of Vibrio cholerae and Escherichia coli heat-labile enterotoxins is linked to their ADP-ribosyltransferase activity. European Journal of Immunology 22: 22772281.CrossRefGoogle ScholarPubMed
Ma, XJ, Chow, JM, Gri, G, Carra, G, Gerosa, F, Wolf, SE, Dzialo, R and Trinchieri, G (1996). The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells. Journal of Experimental Medicine 183: 147157.Google Scholar
Ma, XJ, Neurath, M, Gri, G and Trinchieri, G (1997). Identification and characterization of a novel ets-2-related nuclear complex implicated in the activation of the human interleukin-12 p40 gene promoter. Journal of Biological Chemistry 272: 1038910395.Google Scholar
Macatonia, SE, Hosken, NA, Litton, M, Vieira, P, Hsieh, CS, Culpepper, JA, Wysocka, M, Trinchieri, G, Murphy, KM and O'Garra, A (1995). Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4(+) T cells. Journal of Immunology 154: 50715079.Google Scholar
MacDonald, TT (1983). Immunosuppression caused by antigen feeding II. Suppressor T cells mask Peyer's patch B cell priming to orally administered antigen. European Journal of Immunology 13: 138142.Google Scholar
MacPherson, A, Khoo, UY, Forgacs, I, Philpott-Howard, J and Bjarnason, I (1996). Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut 38: 365375.Google Scholar
Marinaro, M, Staats, HF, Hiroi, T, Jackson, RJ, Coste, M, Boyaka, PN, Okahashi, N, Yamamoto, M, Kiyono, H, Bluethmann, H, Fujihashi, K and McGhee, JR (1995). Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4. Journal of Immunology 155: 46214629.CrossRefGoogle ScholarPubMed
Marinaro, M, Kiyono, H, van Cott, JL, Okahashi, N, van Ginkel, FW, Pascual, DW, Ban, E, Jackson, RJ, Staats, HF and McGhee, JR (1997). Vaccines for selective induction of Th-1 and Th2-cell responses and their roles in mucosal immunity. In: Kagnoff, MF and Kiyono, H (eds) Essentials of Mucosal Immunology. San Diego: Academic Press, pp. 461475.Google Scholar
Marth, T, Strober, W and Kelsall, BL (1996). High dose oral tolerance in ovalbumin TCR-transgenic mice—systemic neutralization of IL-12 augments TGF-beta secretion and T cell apoptosis. Journal of Immunology 157: 23482357.Google Scholar
Mason, HS, Haq, TA, Clements, JD and Arntzen, CJ (1998). Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT)—potatoes expressing a synthetic LT-B gene. Vaccine 16: 13361343.Google Scholar
Mastroeni, P, Harrison, JA, Chabalgoity, JA and Hormaeche, CE (1996). Effect of interleukin 12 neutralization on host resistance and gamma interferon production in mouse typhoid. Infection and Immunity 64: 189196.Google Scholar
Matousek, MP, Nedrud, JG and Harding, CV (1996). Distinct effects of recombinant cholera toxin B subunit and holotoxin on different stages of class II MHC antigen processing and presentation by macrophages. Journal of Immunology 156: 41374145.Google Scholar
Matzinger, P (1994). Tolerance, danger and the extended family. Annual Review of Immunology 12: 9911045.Google Scholar
Mayer, L (1998). Current concepts in mucosal immunity. I. Antigen presentation in the intestine—new rules and regulations. American Journal of Physiology 37: G7-G 9.Google Scholar
McKenzie, SJ and Halsey, JF (1984). Cholera toxin B subunit as a carrier protein to stimulate a mucosal immune response. Journal of Immunology 133: 18181824.Google Scholar
McMenamin, C, Mckersey, M, Kuhnlein, P, Hunig, T and Holt, PG (1995). γδ T cells down-regulate primary IgE responses in rats to inhaled soluble protein antigens. Journal of Immunology 154: 43904394.Google Scholar
Mendoza, RB, Cantwell, MJ and Kipps, TJ (1997). Immunostimulatory effects of a plasmid expressing CD40 ligand (CD154) on gene immunization. Journal of Immunology 159: 57775781.Google Scholar
Mengel, J, Dare, L, Dare, GM, Delgado, M, Nomizo, A, Silva, JS and Campos Neto, A (1992). An activated murine B cell lymphoma line (A-20) produces a factor-like activity which is functionally related to human natural killer cell stimulatory factor. European Journal of Immunology 22: 31733178.Google Scholar
Micallef, MJ, Ohtsuki, T, Kohno, K, Tanabe, F, Ushio, S, Namba, M, Tanimoto, T, Torigoe, K, Fuji, M, Ikeda, M, Fukuda, S and Kurimoto, M (1996). Interferon-gamma-inducing factor enhances T helper 1 cytokine production by stimulated human T cells—synergism with interleukin-12 for interferon-gamma production. European Journal of Immunology 26: 16471651.Google Scholar
Michalek, SM, Eldridge, JH, Curtis, R III and Rosenthal, KL (1994). Antigen delivery systems: new approaches to mucosal immunization. In: Ogra, PA, Mestecky, J, Lamm, ME, Strober, W, McGhee, JR and Bienenstock, J (eds) Handbook of Mucosal Immunology. San Diego: Academic Press, pp. 391402.Google Scholar
Miller, A, Lider, O and Weiner, HL (1991). Antigen-driven bystander suppression after oral administration of antigens. Journal of Experimental Medicine 174: 791798.Google Scholar
Miller, A, Lider, O, Abramsky, O and Weiner, HL (1994). Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals. European Journal of Immunology 24: 10261032.Google Scholar
Miller, BG, Newby, TJ, Stokes, CR and Bourne, FJ (1984). Influence of diet on post weaning malabsorption and diarrhea in the pig. Research in Veterinary Science 36: 187193.Google Scholar
Mondino, A, Khoruts, A and Jenkins, MK (1996). The anatomy of T-cell activation and tolerance. Proceedings of the National Academy of Sciences of the United States of America 93: 22452252.Google Scholar
Monteleone, G, Biancone, L, Marasco, R, Morrone, G, Marasco, O, Luzza, F and Pallone, F (1997). Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology 112: 11691178.CrossRefGoogle ScholarPubMed
Monteleone, G, Trapasso, F, Parrello, T, Biancone, L, Stella, A, Iuliano Luzza, F, Fusco, A and Pallone, F (1999). Bioactive IL-18 expression is up-regulated in Crohn's disease. Journal of Immunology 163: 143147.Google Scholar
Nakagawa, I, Takahashi, I, Kiyono, H, McGhee, JR and Hamada, S (1996). Oral immunization with the B subunit of the heat-labile enterotoxin of Escherichia coli induces early Th1 and late Th2 cytokine expression in Peyer's patches. Journal of Infectious Diseases 173: 14281436.Google Scholar
Nakamura, K, Okamura, H, Nagata, K, Komatsu, T and Tamura, T (1993). Purification of a factor which provides a costimulatory signal for gamma interferon production. Infection and Immunity 61: 6470.Google Scholar
Nashar, TO, Hirst, TR and Williams, NA (1997). Modulation of B-cell activation by the B subunit of Escherichia coli enterotoxin—receptor interaction up-regulates MHC II, B7, CD40, CD25 AND ICAM-1. Immunology 91: 572578.Google Scholar
Noma, T, Yoshizawa, I, Aoki, K, Yamaguchi, K and Baba, M (1996). Cytokine production in children outgrowing hen egg allergy. Clinical and Experimental Allergy 26: 12981307.Google Scholar
Novick, D, Kim, SH, Fantuzzi, G, Reznikov, LL, Dinarello, CA and Rubinstein, M. (1999). Interleukin-18 binding protein: a novel modulator of the Th1 cytokine response. Immunity 10: 127136.Google Scholar
Okamura, H, Nagata, K, Komatsu, T, Tanimoto, T, Nukata, Y, Tanabe, F, Akita, K, Torigoe, K, Okura, T, Fukuda, S and Kurimoto, M (1995 a). A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock. Infection and Immunity 63: 39663972.Google Scholar
Okamura, H, Tsutsui, H, Komatsu, T, Yutsudo, M, Hakura, A, Tanimoto, T, Torigoe, K, Okura, T, Nukada, Y, Hattori, K, Akita, K, Namba, M, Tanabe, F, Konishi, K, Fukuda, S and Kurimoto, M (1995 b). Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378: 8891.Google Scholar
Okamura, H, Tsutsui, H, Kashiwamura, SI, Yoshimoto, T and Nakanishi, K (1998). Interleukin-18: a novel cytokine that augments both innate and acquired immunity. Advances in Immunology 70: 281312.Google Scholar
Olee, T, Hashimoto, S, Quach, J and Lotz, M (1999). IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses. Journal of Immunology 162: 10961100.Google Scholar
Pape, KA, Khoruts, A, Mondino, A and Jenkins, MK (1997). Inflammatory cytokines enhance the in vivo clonal expansion and differentiation of antigen-activated CD4(+) T cells. Journal of Immunology 159: 591598.Google Scholar
Pappo, J and Mahlman, RT (1993). Follicle epithelial M cells are a source of interleukin-1 in Peyer's patches. Immunology 78: 505507.Google Scholar
Parronchi, P, Romagnani, P, Annunziato, F, Sampognaro, S, Becchio, A, Giannarini, L, Maggi, E, Pupilli, C, Tonelli, F and Romagnani, S (1997). Type 1 T-helper cell predominance and interleukin-12 expression in the gut of patients with Crohn's disease. American Journal of Pathology 150: 823832.Google Scholar
Pierce, NF (1978). The role of antigen form and function in the primary and secondary intestinal immune response to cholera toxin and toxoid in rats. Journal of Experimental Medicine 148: 195.CrossRefGoogle ScholarPubMed
Pierce, NF, Cray, WC and Engel, PF (1980). Antitoxic immunity to cholera in dogs immunized orally with cholera toxin. Infection and Immunity 27: 632637.Google Scholar
Pierre, PG, Mbongolo Mbella, EG and Vaerman, JP (1995). Effect of cholera toxin and its B subunit on intestinal permeability for ovalbumin. Advances in Experimental Medicine and Biology 371B: 15191521.Google Scholar
Pirhonen, J, Sareneva, T, Kurimoto, M, Julkunen, I and Matikainen, S (1999). Virus infection activates IL-1 beta and IL-18 production in human macrophages by a caspase-1-dependent pathway. Journal of Immunology 162: 73227329.CrossRefGoogle ScholarPubMed
Pizarro, TT, Michie, MH, Bentz, M, Woraratanadharm, J, Smith, MF, Foley, E, Moskaluk, CA, Bickston, SJ and Cominelli, F (1999). IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells. Journal of Immunology 162: 68296835.Google Scholar
Podlaski, FJ, Nanduri, VB, Hulmes, JD, Pan, YC, Levin, W, Danho, W, Chizzonite, R, Gately, MK and Stern, AS (1992 a). Molecular characterization of interleukin 12. Archives of Biochemistry and Biophysics 294: 230237.Google Scholar
Procopio, DO, Teixeira, MM, Camargo, MM, Travassos, LR, Ferguson, MAJ, Almeida, IC and Gazzinelli, RT (1999 b). Differential inhibitory mechanism of cyclic AMP on TNF-alpha and IL-12 synthesis by macrophages exposed to microbial stimuli. British Journal of Pharmacology 127: 11951205.Google Scholar
Quiding, M, Nordstrom, I, Kilander, A, Andersson, G, Hanson, LA, Holmgren, J and Czerkinsky, C (1991). Intestinal immune responses in humans: oral cholera vaccination induces strong intestinal antibody responses and interferon-γ production and evokes local immunologic memory. Journal of Clinical Investigation 88: 143148.Google Scholar
Qureshi, N, Takayama, K and Ribi, E (1982). Purification and structural determination of nontoxic lipid A obtained from lipopolysaccharide of Salmonella typhimurium. Journal of Biological Chemistry 257: 1180811815.Google Scholar
Ramon, G (1925). Sur l'augmentation anormale de l'antitoxine chez les chevaux producteurs de sérum antidiphtérique. Bulletin de la Société Centrale de Médecine Vétérinaire 101: 227.Google Scholar
Rappuoli, R, Pizza, M, Douce, G and Dougan, G (1999). Structure and mucosal adjuvanticity of cholera and Escherichia coli heat-labile enterotoxins. Immunology Today 20: 493500.Google Scholar
Reed, SG, Pihl, DL, Conlon, PJ and Grabstein, KH (1989). IL-1 as adjuvant. Role of T cells in the augmentation of specific antibody production by recombinant human IL-1 alpha. Journal of Immunology 142: 31293133.Google Scholar
Rennick, DM, Fort, MM and Davidson, NJ (1997). Studies with IL-10(–/–) mice—an overview. Journal of Leukocyte Biology. 61: 389396.Google Scholar
Robinson, D, Shibuya, K, Mui, A, Zonin, F, Murphy, E, Sana, T, Hartley, SB, Menon, S, Kastelein, R, Bazan, F and O'Garra, A (1997). IGIF does not drive Th1 development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NK-kappa-B. Immunity 7: 571581.Google Scholar
Rogge, L, Barberismaino, L, Biffi, M, Passini, N, Presky, DH, Gubler, U and Sinigaglia, F (1997). Selective expression of an interleukin-12 receptor component by human T helper 1 cells. Journal of Experimental Medicine 185: 825831.Google Scholar
Rowe, B, Ward, LR and Threlfall, EJ (1997). Multidrug-resistant Salmonella typhi: a worldwide epidemic. Clinical Infectious Diseases 24: S106-S109.Google Scholar
Russell, MW and Wu, HY (1991). Distribution, persistence, and recall of serum and salivary antibody responses to peroral immunization with protein antigen I/II of Streptococcus mutans coupled to the cholera toxin B subunit. Infection and Immunity 59: 40614070.Google Scholar
Russmann, H, Shams, H, Poblete, F, Fu, Y, Galan, JE and Donis, R (1998). Delivery of epitopes by the Salmonella type III secretion system for vaccine development. Science 281: 565568.Google Scholar
Santiago, N, Haas, S and Baughman, RA (1995). Vehicles for oral immunization. In: Powell, MF and Newman, MJ (eds) Vaccine Design: The Subunit and Adjuvant Approach. New York: Plenum Press, pp. 413438.Google Scholar
Schijns, VECJ, Wierda, CMH, Vahlenkamp, TW and Horzinek, MC (1997). Molecular cloning of cat interleukin-12. Immunogenetics 45: 462463.Google Scholar
Schoenhaut, DS, Chua, AO, Wolitzky, AG, Quinn, PM, Dwyer, CM, McComas, W, Familletti, PC, Gately, MK and Gubler, U (1992). Cloning and expression of murine IL-12. Journal of Immunology 148: 34333440.Google Scholar
Schwartz, RH (1996). Models of T cell anergy—is there a common molecular mechanism? Journal of Experimental Medicine 184: 18.Google Scholar
Shanahan, F (1994). The intestinal immune system. In: Johnson, LR (ed.) Physiology of the Gastrointestinal Tract. New York: Raven Press, pp. 643684.Google Scholar
Sieburth, D, Jabs, EW, Warrington, JA, Li, X, Lasota, J, LaForgia, S, Kelleher, K, Huebner, K, Wasmuth, JJ and Wolf, SF (1992). Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5. Genomics 14: 5962.Google Scholar
Snider, DP (1995). The mucosal adjuvant activities of ADP-ribosylating bacterial enterotoxins. Critical Reviews in Immunology 15: 317348.Google Scholar
Snijders, A, Hilkens, CMU, Kraan, TCTMV, Engel, M, Aarden, LA and Kapsenberg, ML (1996). Regulation of bioactive IL-12 production in lipopolysaccharide-stimulated human monocytes is determined by the expression of the p35 subunit. Journal of Immunology 156: 12071212.Google Scholar
Sollid, LM, Kvale, D, Brandtzaeg, P, Markussen, G and Thorsby, E (1987). Interferon-γ enhances expression of secretory component, the epithelial receptor for polymeric immunoglobulins. Journal of Immunology 138: 43034306.Google Scholar
Sone, S, Orino, E, Mizuno, K, Yano, S, Nishioka, Y, Haku, T, Nii, A and Ogura, T (1994). Production of IL-1 and its receptor antagonist is regulated differently by IFN gamma and IL-4 in human monocytes and alveolar macrophages. European Respiratory Journal 7: 657663.Google Scholar
Spangler, BD (1992). Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiological Reviews 56: 622647.Google Scholar
Stern, AS, Podlaski, FJ, Hulmes, JD, Pan, YC, Quinn, PM, Wolitzky, AG, Familletti, PC, Stremlo, DL, Truitt, T, Chizzonite, R and Gately, MK (1990). Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. Proceedings of the National Academy of Sciences of the United States of America 87: 68086812.CrossRefGoogle ScholarPubMed
Stokes, CR, Miller, BG, Bailey, M, Wilson, AD and Bourne, FJ (1987 a). The immune response to dietary antigens and its influence on disease susceptibility in farm animals. Veterinary Immunology and Immunopathology 17: 413423.Google Scholar
Stokes, CR, Miller, BG and Bourne, FJ (1987 b). Animal models of food sensitivity. In: Brostoff, J and Challacombe, SJ (eds) Food Allergy and Intolerance. Philadelphia: Baillière Tindall, pp. 286300.Google Scholar
Stoll, S, Muller, G, Kurimoto, M, Saloga, J, Tanimoto, T, Yamauchi, H, Okamura, H, Knop, J and Enk, AH (1997). Production of IL-18 (IFN-gamma-inducing factor) messenger RNA and functional protein by murine keratinocytes. Journal of Immunology 159: 298302.Google Scholar
Sudo, N, Sawamura, SA, Tanaka, K, Aiba, Y, Kubo, C and Koga, Y (1997). The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. Journal of Immunology 159: 17391745.Google Scholar
Sun, JB, Holmgren, J and Czerkinsky, C (1994). Cholera toxin B subunit: an efficient transmucosal carrier–delivery system for induction of peripheral immunological tolerance. Proceedings of the National Academy of Sciences of the United States of America 91: 1079510799.Google Scholar
Sutas, Y, Autio, S, Rantala, I and Isolauri, E (1997). IFN-γ enhances macromolecular transport across Peyer's patches in suckling rats–implications for natural immune responses to dietary antigens early in life. Journal of Pediatrics, Gastroenterology and Nutrition 24: 162169.Google Scholar
Svennerholm, AM, Jertborn, M, Gothefors, L, Karim, AM, Sack, DA and Holmgren, J (1984). Mucosal antitoxic and antibacterial immunity after cholera disease and after immunization with a combined B subunit-whole cell vaccine. Journal of Infectious Diseases 149: 884893.Google Scholar
Szabo, SJ, Dighe, AS, Gubler, U and Murphy, KM (1997). Regulation of the interleukin (IL)-12R beta-2 subunit expression in developing T helper 1 (Th1) and Th2 cells. Journal of Experimental Medicine 185: 817824.Google Scholar
Sztein, MB, Wasserman, SS, Tacket, CO, Edelman, R, Hone, D, Lindberg, AA and Levine, MM (1994). Cytokine production patterns and lymphoproliferative responses in volunteers orally immunized with attenuated vaccine strains of Salmonella typhi. Journal of Infectious Diseases 170: 15081517.Google Scholar
Sztein, MB, Tanner, MK, Polotsky, Y, Orenstein, JM and Levine, MM (1995). Cytotoxic T lymphocytes after oral immunization with attenuated vaccine strains of Salmonella typhi in humans. Journal of Immunology 155: 39873993.Google Scholar
Tabata, Y, Inoue, Y and Ikada, Y (1996). Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres. Vaccine 14: 16771685.Google Scholar
Tacket, CO, Mason, HS, Losonsky, G, Clements, JD, Levine, MM and Arntzen, CJ (1998). Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato. Nature Medicine 4: 607609.Google Scholar
Takahashi, I, Marinaro, M, Kiyono, H, Jackson, RJ, Nakagawa, I, Fujihashi, K, Hamada, S, Clements, JD, Bost, KL and McGhee, JR (1996). Mechanisms for mucosal immunogenicity and adjuvancy of Escherichia coli labile enterotoxin. Journal of Infectious Diseases 173: 627635.Google Scholar
Takeuchi, M, Nishizaki, Y, Sano, O, Ohta, T, Ikeda, M and Kurimoto, M (1997). Immunohistochemical and immuno-electron-microscopic detection of interferon-gamma-inducing factor (interleukin-18) in mouse intestinal epithelial cells. Cell and Tissue Research 289: 499503.Google Scholar
Taylor, CED (1993). Did vaccinia virus come from a horse? Equine Veterinary Journal 25: 810.Google Scholar
Terpend, K, Boisgerault, F, Blaton, MA, Desjeux, JF and Heyman, M (1998). Protein transport and processing by human ht29–19a intestinal cells—effect of interferon gamma. Gut 42: 538545.Google Scholar
Tizard, IR (1996). Veterinary Immunology. Philadelphia: W.B. Saunders Company.Google Scholar
Tone, Y, Thompson, SAJ, Babik, JM, Nolan, KF, Tone, M, Raven, C and Waldmann, H (1996). Structure and chromosomal location of the mouse interleukin-12 p35 and p40 subunit genes. European Journal of Immunology 26: 12221227.Google Scholar
Trinchieri, G (1998). Interleukin-12: a cytokine at the interface of inflammation and immunity. Advances in Immunology 70: 83243.Google Scholar
Tsuji, T, Hamajima, K, Fukushima, J, Xin, KQ, Ishii, N, Aoki, I, Ishigatsubo, Y, Tani, K, Kawamoto, S, Nitta, Y, Miyazaki, J, Koff, WC, Okubo, T and Okuda, K (1997). Enhancement of cell-mediated immunity against HIV-1 induced by coinoculation of plasmid-encoded HIV-1 antigen with plasmid expressing IL-12. Journal of Immunology 158: 40084013.Google Scholar
Tsutsui, H, Kayagaki, N, Kuida, K, Nakano, H, Hayashi, N, Takeda, K, Matsui, K, Kashiwamura, S, Hada, T, Akira, S, Yagita, H, Okamura, H and Nakanishi, K (1999). Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. Immunity 11: 359367.Google Scholar
Umesaki, Y and Setayama, H (1992). Immune response of mice to orally administered asialo GM1-specific rabbit IgG in the presence or absence of cholera toxin. Immunology 75: 386386.Google Scholar
Urban, JF, Fayer, R, Chen, SJ, Gause, WC, Gately, MK and Finkelman, FD (1996). IL-12 protects immunocompetent and immunodeficient neonatal mice against infection with Cryptosporidium parvum. Journal of Immunology 156: 263268.Google Scholar
Ushio, S, Namba, M, Okura, T, Hattori, K, Nukada, Y, Akita, K, Tanabe, F, Konishi, K, Micallef, M, Fujii, M, Torigoe, K, Tanimoto, T, Fukuda, S, Ikeda, M, Okamura, H and Kurimoto, M (1996). Cloning of the cDNA for human IFN-gamma-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein. Journal of Immunology 156: 42744279.Google Scholar
Vajdy, M, Kosco-Vilbois, MH, Kopf, M, Kohler, G and Lycke, N (1995). Impaired mucosal immune responses in interleukin 4-targeted mice. Journal of Experimental Medicine 181: 4153.CrossRefGoogle ScholarPubMed
Van den Broeck, WCox, E and Goddeeris, BM (1999). Induction of immune responses in pigs following oral administration of purified F4 fimbriae. Vaccine 17: 20202029.Google Scholar
VanCott, JL, Staats, HF, Pascual, DW, Roberts, M, Chatfield, SN, Yamamoto, M, Coste, M, Carter, PB, Kiyono, H and McGhee, JR (1996). Regulation of mucosal and systemic antibody responses by T helper cell subsets, macrophages, and derived cytokines following oral immunization with live recombinant Salmonella. Journal of Immunology 156: 15041514.Google Scholar
Vanhouten, N and Blake, SF (1996). Direct measurement of anergy of antigen-specific T cells following oral tolerance induction. Journal of Immunology 157: 13371341.Google Scholar
Vaz, N, Faria, AMC, Verdolin, BA and Carvalho, CR (1997). Immaturity, ageing and oral tolerance. Scandinavian Journal of Immunology 46: 225229.Google Scholar
Vella, AT, Mitchell, T, Groth, B, Linsley, PS, Green, JM, Thompson, CB, Kappler, JW and Marrack, P (1997). CD28 engagement and proinflammatory cytokines contribute to T cell expansion and long-term survival in vivo. Journal of Immunology 158: 47144720.Google Scholar
Villinger, F, Brar, SS, Mayne, A, Chikkala, N and Ansari, AA (1995). Comparative sequence analysis of cytokine genes from human and nonhuman primates. Journal of Immunology 155; 39463954.Google Scholar
Vogel, FR and Powell, MF (1995). A compendium of vaccine adjuvants and excipients. In: Powell, MF and Newman, MJ (eds) Vaccine Design: The Subunit and Adjuvant Approach. New York: Plenum Press, pp. 141228.Google Scholar
Waldor, MK and Mekalanos, JJ (1994). Emergence of a new cholera pandemic: molecular analysis of virulence determinants in Vibrio cholerae O139 and development of a live vaccine prototype. Journal of Infectious Diseases 170: 278283.CrossRefGoogle ScholarPubMed
Wassen, L, Schon, K, Holmgren, J, Jertborn, M and Lycke, N (1996). Local intravaginal vaccination of the female genital tract. Scandinavian Journal of Immunology 44: 408414.Google Scholar
Weigle, WO, Scheuer, WV, Hobbs, MV, Morgan, EL and Parks, DE (1987). Modulation of the induction and circumvention of immunological tolerance to human gamma-globulin by interleukin 1. Journal of Immunology 138: 20692074.Google Scholar
Weiner, HL (1997). Oral tolerance—immune mechanisms and treatment of autoimmune diseases. Immunology Today 18: 335343.Google Scholar
Weiner, HL, Friedman, A, Miller, A, Khoury, SJ, Al-Sabbagh, A, Santos, L, Sayegh, M, Nussenblatt, RB, Trentham, DE and Hafler, DA (1994). Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annual Review of Immunology 12: 809837.Google Scholar
Wells, HG and Osborne, TB (1911). The biological reactions of the vegetable proteins. Journal of Infectious Diseases 8: 66124.Google Scholar
Wilson, AD, Stokes, CR and Bourne, FJ (1989). Adjuvant effect of cholera toxin on the mucosal immune response to soluble proteins. Differences between mouse strains and protein antigens. Scandinavian Journal of Immunology 29: 739745.Google Scholar
Wilson, AD, Clark, CJ and Stokes, CR (1990). Whole cholera toxin and B subunit act synergistically as an adjuvant for the mucosal immune response in mice to keyhole limpet haemocyanin. Scandinavian Journal of Immunology 31: 443451.Google Scholar
Wolf, SF, Temple, PA, Kobayashi, M, Young, D, Dicig, M, Lowe, L, Dzialo, R, Fitz, L, Ferenz, C, Hewick, RM, Kelleher, K, Herrman, SH, Clark, SC, Azzoni, L, Chan, SH, Trinchieri, G and Perussia, B (1991). Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. Journal of Immunology 146: 30743081.Google Scholar
World Health Organization (1997). The World Health Report 1996: Fighting Disease, Fostering Development. Geneva: World Health Organization.Google Scholar
Xuamano, JC, Jackson, RJ, Fujihashi, K, Kiyono, H, Staats, HF and McGhee, JR (1994). Helper Th1 and Th2 cell responses following mucosal or systemic immunization with cholera toxin. Vaccine 12: 903911.Google Scholar
Yamane, H, Kato, T and Nariuchi, H (1999). Effective stimulation for IL-12 p35 mRNA accumulation and bioactive IL-12 production of antigen-presenting cells interacted with Th cells. Journal of Immunology 162: 64336441.Google Scholar
Yoshimoto, T, Kojima, K, Funakoshi, T, Endo, Y, Fujita, T and Nariuchi, H (1996). Molecular cloning and characterization of murine IL-12 genes. Journal of Immunology 156: 10821088.Google Scholar
Yoshimoto, T, Takeda, K, Tanaka, T, Ohkusu, K, Kashiwamura, S, Okamura, H, Akira, S and Nakanishi, K (1998). IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells—synergism with IL-18 for IFN-gamma production. Journal of Immunology 161: 34003407.Google Scholar
Zarlenga, DS, Canals, A, Aschenbrenner, RA and Gasbarre, LC (1995). Enzymatic amplification and molecular cloning of cDNA encoding the small and large subunits of bovine interleukin 12. Biochimica et Biophysica Acta 1270: 215217.Google Scholar