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

Resistance to the murine intestinal nematode Trichuris muris requires the d evelopment of a strong Th2 response. In a reconstituted SCID mouse model, C D4(+) Th2 cells can mediate resistance to infection in the absence of antib ody (Else & Grencis, 1996). The data presented here address the issue of ho w CD4(+) T cells mediate this protective immunity within the SCID host. The se studies demonstrate that timing and cell dose are critical if transfer i s to result in resistance, with a minimum of 5 x 10(6) immune donor cells r equired to confer immunity. Furthermore, this CD4-mediated protective immun ity only operates against the larval stages of the parasite. When the molec ules necessary for activated CD4(+) T cell migration to the GALT are inhibi ted with a cocktail of anti-integrin/addressin antibodies (anti-beta7, anti -MAdCAM-1 and anti-alphaE), the resistance conferred by immune donor cells is completely abrogated. This implies that the effector mechanism acts loca lly at the level of the gut. CD4(+) mediated cytotoxicity, directed against the epithelial cells inhabited by the parasite, could represent a novel, l ocally acting effector mechanism. However, Fas and Fas ligand-deficient mic e, which are unable to mount CD4-mediated cytotoxic responses, readily expe l T. muris indicating that the mechanism by which CD4(+) T cells mediate pr otective immunity is unlikely to involve killing of infected gut epithelial cells.