Resolution of leishmaniasis depends upon parasite control and limiting inflammation. CD4 Th1 cells are required to control parasites, whereas CD8 T cells play a dual role: they promote Th1 cell differentiation but can also increase inflammation at the site of infection as a consequence of cytolysis. Although CD8 T cells taken from leishmanial lesions are cytolytic, in this study, we showed that only a few CD8 T cells produced IFN-γ. Correspondingly, only low levels of IL-12 and/or IL-12 mRNA were present in lesions from infected mice, as well as patients. Addition of IL-12 increased IFN-γ production by CD8 T cells isolated from leishmanial lesions, suggesting that a lack of IL-12 at the site of infection limits IFN-γ production by CD8 T cells. To determine whether CD8 T cells could promote resistance in vivo if IL-12 was present, we administered IL-12 to -infected RAG mice reconstituted with CD8 T cells. IL-12 treatment increased the ability of CD8 T cells to make IFN-γ, but CD8 T cells still failed to control the parasites. Furthermore, despite the ability of CD8 T cells to promote immunity to secondary infections, we also found that CD8 T cells from immune mice were unable to control in RAG mice. Taken together, these results indicate that lesional CD8 T cells fail to make IFN-γ because of a deficit in IL-12 but that, even with IL-12, CD8 T cells are unable to control in the absence of CD4 T cells.
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