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Infect Immun ; 83(3): 898-906, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25534940

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.


Subject(s)
CD4-Positive T-Lymphocytes/pathology , Leishmania braziliensis/pathogenicity , Leishmaniasis, Cutaneous/pathology , T-Lymphocytes, Cytotoxic/pathology , Amino Acid Chloromethyl Ketones/pharmacology , Antigens, Protozoan/immunology , Antigens, Protozoan/pharmacology , Apoptosis/drug effects , Asymptomatic Diseases , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , Chronic Disease , Coculture Techniques , Cytotoxicity, Immunologic , Enzyme Inhibitors/pharmacology , Granzymes/antagonists & inhibitors , Granzymes/metabolism , Humans , Interferon-gamma/biosynthesis , Interferon-gamma/metabolism , Leishmania braziliensis/immunology , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/parasitology , Lymphocyte Count , Monocytes/immunology , Monocytes/parasitology , Primary Cell Culture , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Cytotoxic/immunology , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/metabolism
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