PROTECTION OF MICE AGAINST TRYPANOSOMA-CRUZI BY IMMUNIZATION WITH PARAFLAGELLAR ROD PROTEINS REQUIRES T-CELL, BUT NOT B-CELL, FUNCTION

Previous studies have shown that immunization of mice with the parafla gellar rod proteins (PAR) of Trypanosoma cruzi induces an immune respo nse capable of protecting mice against an otherwise lethal challenge w ith this parasite. Herein, we define immunologic responses that do or do not play a critical role in PAR-mediated protection. Firstly, PAR-i mmunized Ab-deficient (mu MT) strain mice survived an otherwise lethal T. cruzi challenge, indicating that a B cell response is not required for PAR-induced immunity. However, beta(2)m -/- mice, which are sever ely deficient in MHC class I and TCR alpha beta(+)CD8(+)CD4(-) T cells , did not survive challenge infection following PAR immunization, indi cating that MHC class I/CD8(+) T cell function is necessary for protec tion induced by PAR immunization. Surprisingly, PAR-immunized mice dep leted of CD4(+) T cells survived a T. cruzi challenge for >84 days pos tinfection while maintaining a parasitemia that is generally thought t o be lethal (i.e., > 10(6) trypomastigotes/ml), thus associating CD4() T cell function with the process of parasite clearance. Consistent w ith this association, CD4(+) T cells from PAR-immunized mice released INF-gamma and stimulated T. cruzi-infected macrophages to release nitr ic oxide. The importance of IFN-gamma in PAR-induced protective immuni ty is further indicated by the observation that PAR-immunized INF-gamm a knockout mice developed an extremely high parasitemia and did not su rvive a challenge infection. Thus, while Ab-mediated immune mechanisms are not required for protection induced by PAR immunization, T cell r esponses are necessary for both elimination of bloodstream parasites a nd survival.