CD8+ T Cells Lack Local Signals To Produce IFN-γ in the Skin during Leishmania Infection.
J Immunol
; 200(5): 1737-1745, 2018 03 01.
Article
em En
| MEDLINE
| ID: mdl-29367210
ABSTRACT
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 Leishmania-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 Leishmania 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 Leishmania in the absence of CD4+ T cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pele
/
Interferon gama
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Leishmaniose Cutânea
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Linfócitos T CD8-Positivos
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Leishmania
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article