Predominant role of interferon-γ in the host protective effect of CD8+ T cells against Neospora caninum infection

It is well established that CD8(+) T cells play an important role in protective immunity against protozoan infections. However, their role in the course of Neospora caninum infection has not been fully elucidated. Here we report that CD8-deficient mice infected with N. caninum presented higher parasitic loads in the brain and lungs and lower spleen and brain immunity-related GTPases than their wild-type counterparts. Moreover, adoptive transfer of splenic CD8(+) T cells sorted from N. caninum-primed immunosufficient C57BL/10 ScSn mice prolonged the survival of infected IL-12-unresponsive C57BL/10 ScCr recipients. In both C57BL/6 and C57BL/10 ScSn mice CD8(+) T cells are activated and produce interferon-gamma (IFN-gamma) upon challenged with N. caninum. The host protective role of IFN-gamma produced by CD8(+) T cells was confirmed in N. caninum-infected RAG2-deficient mice reconstituted with CD8(+) T cells obtained from either IFN-gamma-deficient or wild-type donors. Mice receiving IFN-gamma-expressing CD8(+) T cells presented lower parasitic burdens than counterparts having IFN-gamma-deficient CD8(+) T cells. Moreover, we observed that N. caninum-infected perforin-deficient mice presented parasitic burdens similar to those of infected wild-type controls. Altogether these results demonstrate that production of IFN-gamma is a predominant protective mechanism conferred by CD8(+) T cells in the course of neosporosis.