biostudies-literatureNovais FONIAID NIH HHS1737-1745https://www.ebi.ac.uk/biostudies/studies/S-EPMC6178231biostudies-literatureUnknown200(5)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-?. 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-? production by CD8+ T cells isolated from leishmanial lesions, suggesting that a lack of IL-12 at the site of infection limits IFN-? 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 Leishmania-infected RAG mice reconstituted with CD8+ T cells. IL-12 treatment increased the ability of CD8+ T cells to make IFN-?, 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 Leishmania in RAG mice. Taken together, these results indicate that lesional CD8+ T cells fail to make IFN-? because of a deficit in IL-12 but that, even with IL-12, CD8+ T cells are unable to control Leishmania in the absence of CD4+ T cells.Journal of immunology (Baltimore, Md. : 1950)CD8+ T Cells Lack Local Signals To Produce IFN-? in the Skin during Leishmania Infection.PMC6178231R01 AI106842Villareal DOWong ACScott PNovais FOBeiting DPfalseCD8+ T Cells Lack Local Signals To Produce IFN-? in the Skin during Leishmania Infection.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-?. 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-? production by CD8+ T cells isolated from leishmanial lesions, suggesting that a lack of IL-12 at the site of infection limits IFN-? 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 Leishmania-infected RAG mice reconstituted with CD8+ T cells. IL-12 treatment increased the ability of CD8+ T cells to make IFN-?, 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 Leishmania in RAG mice. Taken together, these results indicate that lesional CD8+ T cells fail to make IFN-? because of a deficit in IL-12 but that, even with IL-12, CD8+ T cells are unable to control Leishmania in the absence of CD4+ T cells.2018-01-01T00:00:00Z2018 Mar2020-11-19T16:31:24Z2019-06-06T20:16:55ZS-EPMC61782312936721010.4049/jimmunol.1701597