(aqui)
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 the 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 to PBMC. Upon L. braziliensis-restimulation, most of 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 significant higher percentage of TUNEL-positive cells and granzyme B expression in the biopsies of patients showing a more intense necrotic process.
Furthermore, co-culture of infected macrophages and CD8+T lymphocytes resulted in 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, co- culture 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 cutaneous leishmaniasis: CD8+ Granzyme B+T cells mediate tissue injury whereas CD4+ IFN-γ+T cells mediate 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 to PBMC. Upon L. braziliensis-restimulation, most of 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 significant higher percentage of TUNEL-positive cells and granzyme B expression in the biopsies of patients showing a more intense necrotic process.
Furthermore, co-culture of infected macrophages and CD8+T lymphocytes resulted in 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, co- culture 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 cutaneous leishmaniasis: CD8+ Granzyme B+T cells mediate tissue injury whereas CD4+ IFN-γ+T cells mediate parasite killing.
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