Trichuris muris: CD4⁺ T cell-mediated protection in reconstituted SCID mice

Abstract

Resistance to the murine intestinal nematode Trichuris muris requires the development of a strong Th2 response. In a reconstituted SCID mouse model, CD4⁺ Th2 cells can mediate resistance to infection in the absence of antibody (Else & Grencis, 1996). The data presented here address the issue of how CD4⁺ T cells mediate this protective immunity within the SCID host. These studies demonstrate that timing and cell dose are critical if transfer is to result in resistance, with a minimum of 5 × 10⁶ immune donor cells required to confer immunity. Furthermore, this CD4-mediated protective immunity only operates against the larval stages of the parasite. When the molecules necessary for activated CD4⁺ T cell migration to the GALT are inhibited with a cocktail of anti-integrin/addressin antibodies (anti-β7, anti-MAdCAM-1 and anti-αE), the resistance conferred by immune donor cells is completely abrogated. This implies that the effector mechanism acts locally at the level of the gut. CD4⁺ mediated cytotoxicity, directed against the epithelial cells inhabited by the parasite, could represent a novel, locally acting effector mechanism. However, Fas and Fas ligand-deficient mice, which are unable to mount CD4-mediated cytotoxic responses, readily expel T. muris indicating that the mechanism by which CD4⁺ T cells mediate protective immunity is unlikely to involve killing of infected gut epithelial cells.