4.6 Article

CD8(+) T Cells Lack Local Signals To Produce IFN-gamma in the Skin during Leishmania Infection

Journal

JOURNAL OF IMMUNOLOGY
Volume 200, Issue 5, Pages 1737-1745

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1701597

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Funding

  1. National Institutes of Health/National Institute of Allergy and Infectious Diseases [R01 AI 106842]
  2. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI106842] Funding Source: NIH RePORTER

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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-g. Correspondingly, only low levels of IL-12 and/or IL-12 mRNAwere present in lesions from infected mice, as well as patients. Addition of IL-12 increased IFN-g production by CD8(+) T cells isolated from leishmanial lesions, suggesting that a lack of IL-12 at the site of infection limits IFN-g 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-g, 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-g 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.

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