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CD8(+) GRANZYME B(+)-MEDIATED TISSUE INJURY VS. CD4(+)IFNγ(+)-MEDIATED PARASITE KILLING IN HUMAN CUTANEOUS LEISHMANIASIS
Leishmaniose Cutânea
Biomarcadores
Linfócitos T CD8 positivos
Linfócitos T CD4 positivos
Humanos
Adulto
Adolescente
Leishmaniasis, Cutaneous
Biomarkers
CD8-Positive T-Lymphocytes
CD4-Positive T-Lymphocytes
Humans
Adult
Adolescent
Autor(es)
Afiliação
Resumo em Inglês
A protective or deleterious role of CD8(+)T cells in human cutaneous leishmaniasis (CL) has been debated. The present report explores the participation of CD8(+)T cells in disease pathogenesis as well as in parasite killing. CD8(+)T cells accumulated in CL lesions as suggested by a higher frequency of CD8(+)CD45RO(+)T cells and CD8(+)CLA(+)T cells compared with peripheral blood mononuclear cells. Upon Leishmania braziliensis restimulation, most of the CD8(+)T cells from the lesion expressed cytolytic markers, CD107a and granzyme B. Granzyme B expression in CL lesions positively correlated with lesion size and percentage of TUNEL-positive cells. We also observed a significantly higher percentage of TUNEL-positive cells and granzyme B expression in the biopsies of patients showing a more intense necrotic process. Furthermore, coculture of infected macrophages and CD8(+)T lymphocytes resulted in the release of granzyme B, and the use of granzyme B inhibitor, as well as z-VAD, Fas:Fc, or anti-IFN-γ, had no effect upon parasite killing. However, coculture of infected macrophages with CD4(+)T cells strongly increased parasite killing, which was completely reversed by anti-IFN-γ. Our results reveal a dichotomy in human CL: CD8(+) granzyme B(+)T cells mediate tissue injury, whereas CD4(+)IFN-γ(+)T cells mediate parasite killing.
Palavras-chave
Leishmania braziliensisLeishmaniose Cutânea
Biomarcadores
Linfócitos T CD8 positivos
Linfócitos T CD4 positivos
Humanos
Adulto
Adolescente
Palavras-chave em inglês
Leishmania braziliensisLeishmaniasis, Cutaneous
Biomarkers
CD8-Positive T-Lymphocytes
CD4-Positive T-Lymphocytes
Humans
Adult
Adolescent
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