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Protective and Pathological Functions of CD8+ T Cells in Leishmania braziliensis Infection
Authors:Thiago Marconi Cardoso   álvaro Machado  Diego Luiz Costa  Lucas P. Carvalho  Adriano Queiroz  Paulo Machado  Phillip Scott  Edgar M. Carvalho  Olívia Bacellar
Abstract:
Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is characterized by a strong Th1 response that leads to skin lesion development. In areas where L. braziliensis transmission is endemic, up to 15% of healthy subjects have tested positive for delayed-type hypersensitivity to soluble leishmania antigen (SLA) and are considered to have subclinical (SC) infection. SC subjects produce less gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) than do CL patients, but they are able to control the infection. The aim of this study was to characterized the role of CD8+ T cells in SC infection and in CL. Peripheral blood mononuclear cells (PBMC) were stimulated with SLA to determine the frequencies of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells. Monocytes from PBMC were infected with L. braziliensis and cocultured with CD8+ T cells, and the frequencies of infected monocytes and levels of cytotoxicity markers, target cell apoptosis, and granzyme B were determined. The frequency of CD8+ IFN-γ+ cells after SLA stimulation was higher for SC individuals than for CL patients. The frequency of infected monocytes in SC cells was lower than that in CL cells. CL CD8+ T cells induced more apoptosis of infected monocytes than did SC CD8+ T cells. Granzyme B production in CD8+ T cells was higher in CL than in SC cells. While the use of a granzyme B inhibitor decreased the number of apoptotic cells in the CL group, the use of z-VAD-FMK had no effect on the frequency of these cells. These results suggest that CL CD8+ T cells are more cytotoxic and may be involved in pathology.
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