Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-24T06:24:42.833Z Has data issue: false hasContentIssue false

Iron deficiency and in vitro iron chelation reduce the expression of cluster of differentiation molecule (CD)28 but not CD3 receptors on murine thymocytes and spleen cells

Published online by Cambridge University Press:  07 June 2007

Solo R. Kuvibidila*
Affiliation:
Department of Pediatrics, Division of Hematology/Oncology, Box T8-1, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, New Orleans LA 70112, USA
Connie Porretta
Affiliation:
Department of Medicine, Section of Pulmonary Medicine, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, New Orleans LA 70112, USA
*
*Corresponding author: Dr Solo Kuvibidila, fax +1 508 568 3078, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Cluster of differentiation molecule (CD)3 and CD28 receptors play crucial roles in T-lymphocyte proliferation. Fe deficiency in man and animals impairs T-lymphocyte proliferation by unknown mechanisms. To test the hypothesis that reduced CD3 and CD28 expression is one of them, thymocytes and splenocytes from control (C; n 24), Fe-deficient (ID; n 24), pair-fed (PF; n 24), and ID mice that were Fe-repleted for 3 (R3; n 24) or 14d (R14; n 12) were labelled with anti-CD3-fluorescein isothiocyanate and anti-CD28-phycoerythrin antibodies. Positive cells were analysed by flow cytometry. Significant differences were observed among groups in the mean levels of haemoglobin and liver Fe stores (C=PF=R14>R3>ID; P<0·005). While Fe deficiency slightly increased the percentage of CD3+ splenocytes, it reduced that of CD28+ thymocytes in mice with thymus atrophy and splenomegaly (P<0·05). These changes were corrected by Fe repletion. CD28 mean fluorescence intensity (FI) was lower and CD3 FI was higher in lymphocytes from R3 and ID, especially those with splenomegaly, than in those from R14 and PF mice (P<0·05). In vitro Fe chelation by deferoxamine (60min) significantly decreased CD28 expression (P<0·05), and slightly increased that of CD3 (P>0·05). Spleen cell proliferative responses to concanavalin A and anti-CD3±anti-CD28 were reduced by Fe deficiency (ID≤R3<C=PF<R14; P<0·05); and they correlated with FI and percentages of CD3+ and CD28+ cells (r≤0·69; P<0·05). Indicators of Fe status negatively correlated with CD3 FI (r−0·23), but positively correlated with CD28 FI (r≤0·44; P<0·05). Data suggest that altered CD28 expression may contribute to reduced T-cell proliferation during Fe deficiency.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2003

References

Abbas, AK, Lichtman, AH & Pober, JS (1997) T lymphocyte antigen recognition and activation. In Cellular and Molecular Immunology. pp 138170. [Abbas, AK, Lichtman, AH and Pober, JS, editors]. Philadelphia, PA: WB Saunders Company.Google Scholar
Chandra, RK & Saraya, AK (1975) Immunocompetence associated with iron deficiency. J Pediatr 86, 899902.CrossRefGoogle ScholarPubMed
Dhur, A, Galan, P, Preziosi, P & Hercberg, S (1991) Lymphocyte subpopulations in the thymus, lymph nodes, and spleen of iron-deficient and rehabilitated mice. J Nutr 121, 14181424.Google Scholar
Furukawa, T, Naitoh, Y, Kohno, H, Tokinaga, R & Taketani, S (1992) Iron deprivation decreases ribonucleotide reductase and DNA synthesis. Life Sci 50, 20592065.Google Scholar
Galan, P, Thibault, H, Preziosi, P & Hercberg, S (1992) Interleukin-2 production in iron-deficient children. Biol Trace Elem Res 32, 421426.CrossRefGoogle ScholarPubMed
Gross, JA, Callas, E & Allison, JP (1992) Identification and distribution of the co-stimulatory receptor CD28 in the mouse. J Immunol 149, 380388.CrossRefGoogle Scholar
Haq, RU, Wereley, JP & Chitambar, C (1995) Induction of apoptosis by iron deprivation in human leukemic CCCRI-CEM cells. Exp Hematol 23, 428432.Google Scholar
Harding, FA, McArthur, JG, Gross, JA, Raulet, DH & Allison, JP (1992) CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 356, 607609.CrossRefGoogle ScholarPubMed
Hathcock, KS, Laslo, G, Pucillo, C, Linsley, P & Hodes, RJ (1994) Comparative analysis of B7-1 and B7-2 co-stimulatory ligands: expression and function. J Exp Med 180, 631640.CrossRefGoogle Scholar
Havran, WL, Poenie, M & Kimura, J (1987) Expression and function of the CD3-antigen receptor on murine CD4+8+ thymocytes. Nature 330, 170173.Google Scholar
Hileti, D, Panayiotidis, P & Hoffbrand, AV (1995) Iron chelators induce apoptosis in proliferating cells. Br J Haematol 89, 181187.CrossRefGoogle ScholarPubMed
June, CH, Bluestone, JA, Nadler, LM & Thompson, CB (1994) The B7 and CD28 receptor families. Immunol Today 15, 321331.Google Scholar
June, CH, Ledbetter, JA, Linsley, PS & Thompson, CB (1990) Role of the CD28 receptor in T-cell activation. Immunol Today 11, 211216.Google Scholar
Kemahli, AS, Babacan, E & Cavdar, AO (1988) Cell-mediated immune responses in children with iron deficiency and combined with iron and zinc deficiency. Research 8, 129136.Google Scholar
Kuvibidila, S, Dardenne, M, Savino, W & Lepol, F (1990) Influence of iron deficiency anaemia on selected thymus functions in mice: thymulin biological activity, T-cell subsets, and thymocyte proliferation. Am J Clin Nutr 51, 228232.CrossRefGoogle ScholarPubMed
Kuvibidila, S, Nauss, KM, Baliga, BS & Suskind, RM (1983) Impairment of blastogenic response of splenic lymphocytes from iron deficient mice: in vivo repletion. Am J Clin Nutr 37, 1525.CrossRefGoogle ScholarPubMed
Kuvibidila, S & Porretta, C (2002) Differential effects of iron deficiency on the expression of CD80 and CD86 co-stimulatory receptors in mitogen-treated and untreated murine spleen cells. J Cell Biochem 86, 571582.CrossRefGoogle ScholarPubMed
Kuvibidila, S & Sarpong, D (1990) Mitogenic response of lymph nodes and spleen cells from mice with moderate and severe iron deficiency. Nutr Res 10, 195210.Google Scholar
Kuvibidila, SR, Baliga, BS, Warrier, RP & Suskind, RM (1998) Iron deficiency reduces the hydrolysis of cell membrane phosphatidyl-inositol 4,5 bis-phosphate during splenic lymphocyte activation in C57BL/6 mice. J Nutr 128, 10771083.Google Scholar
Kuvibidila, SR, Kitchens, D & Baliga, BS (1999) In vivo and in vitro iron-deficiency reduces protein kinase C activity and translocation in murine splenic and purified T cells. J Cell Biochem 74, 468478.Google Scholar
Kuvibidila, SR, Porretta, C, Baliga, BS & Leiva, LE (2001) Reduced thymocyte proliferation but not increased apoptosis as a cause of thymus atrophy in iron-deficient mice. Br J Nutr 86, 157162.Google Scholar
Latunde-Dada, GO & Young, AP (1992) Iron deficiency and immune response. Scand J Immunol 11, 207209.Google Scholar
Looker, AC, Dallman, PR, Carroll, MD, Gunter, EW & Johnson, CL (1997) Prevalence of iron deficiency in the United States. JAMA 277, 973976.CrossRefGoogle ScholarPubMed
Munro, HB (1993) Differences among group means: one way analysis of variance. In Statistical Methods for Health Care Research, 2nd ed., pp 99128. [Munro, HB and Page, EB, editors]. Philadelphia, PA: JB Lippincott Company.Google Scholar
Polson, RJ, Jenkins, R & Lombard, M (1990) Mechanisms of inhibition of mononuclear cell activation by the iron-deficient desferrioxamine. Immunology 71, 176181.Google Scholar
Rodak, BF (1992) Routine laboratory evaluation of erythrocytes. In Clinical Hematology, Principles, Procedures, Correlations, pp 107123. [Lotspeich-Steininger, CA, Stiene-Martin, EA and Koepke, JA, editors]. Philadelphia, PA: J.B. Lippincott Company.Google Scholar
Santos, M & De Sousa, M (1994) In vitro modulation of T-cell surface molecules by iron. Cell Immunol 154, 498506.Google Scholar
Shahinian, T, Pfeffer, K & Lee, PK (1993) Differential T cell co-stimulatory requirements in CD28-deficient mice. Science 261, 609612.CrossRefGoogle Scholar
Thompson, CB, Lindsten, T & Ledbetter, JA (1989) CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci USA 86, 13331337.Google Scholar
Turka, LA, Ledbetter, JA, Lee, K, June, CH & Thompson, CB (1990) CD28 is an inducible T cell surface antigen that transduces a proliferative signal in CD3+ mature thymocytes. J Immunol 144, 16461653.Google Scholar
Turka, LA, Linsley, PS, Paine, R III, et al. (1991) Signal transduction via CD4, CD8, and CD28 in mature and immature thymocytes: Implications for thymus selection. J Immunol 146, 14281436.Google Scholar