| First Author | Novais FO | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 5 | Pages | 1737-1745 |
| PubMed ID | 29367210 | Mgi Jnum | J:258426 |
| Mgi Id | MGI:6117889 | Doi | 10.4049/jimmunol.1701597 |
| Citation | Novais FO, et al. (2018) CD8(+) T Cells Lack Local Signals To Produce IFN-gamma in the Skin during Leishmania Infection. J Immunol 200(5):1737-1745 |
| abstractText | 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-gamma. 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-gamma production by CD8(+) T cells isolated from leishmanial lesions, suggesting that a lack of IL-12 at the site of infection limits IFN-gamma 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-gamma, 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-gamma 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. |
