Prolongation of allograft survival by Nippostrongylus brasiliensis is associated with decreased allospecific cytotoxic T lymphocyte activity and development of T cytotoxic cell type 2 cells

Background, We have demonstrated that infection with Nippostrongylus brasil iensis (Nb), which induces strong type 2 responses, prolongs kidney allogra ft survival in rats. Here, we confirm that this effect is not species-speci fic and address immune modulation in allospecific T-cell responses mediated by nematode infection. Methods. C57BL/6 mice were injected with Nb or phosphate-buffered saline. F our days later, mice were transplanted with BALB/c hearts and graft surviva l was assessed. In other experiments, Nb-infected mice were immunized with BALB/c spleen cells and allospecific T-cell responses were determined in vi tro. Results. In this study, we show that Nb prolongs cardiac allograft survival in mice. Further, spleen T cells from Nb-infected, allo-immunized mice exh ibit reduced allospecific cytotoxic T-lymphocyte activity. In contrast, all ospecific proliferation of T cells in the mixed lymphocyte reaction was not reduced by Nb, ruling out immunosuppression as the mechanism of Nb-induced allograft survival. Nb infection induced IL-4 and IL-6 and inhibited IFN-g amma production by T cells in response to allo-antigen. Furthermore, anti-I L-4 treatment reduced allospecific T-cen proliferation from Nb-infected but not control mice, indicating that type 2 allospecific T cells develop in t he presence of Nb. We also double-stained T cells for CD8 and IL-4 and show ed that Nb induces an 8-fold increase in Tc2 cell numbers. Conclusions. These results are consistent with a hypothesis that Nb mediate s prolongation of allograft survival through induction of type 2 immunity, including the development of regulatory Tc2 cells, and subsequent inhibitio n of allospecific cytotoxic T-lymphocyte activity.