title: Protective and pathological functions of CD8+ T cells in Leishmania braziliensis infection.
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.
authors.affiliation: Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT) (CNPq/MCT), Salvador, BA, Brazil.
authors.forename: Thiago Marconi
authors.initials: TM
authors.lastname: Cardoso
authors.affiliation: Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Machado
authors.affiliation: Departamento de Farmacologia, Escola de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Diego Luiz
authors.initials: DL
authors.lastname: Costa
authors.affiliation: Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT) (CNPq/MCT), Salvador, BA, Brazil.
authors.forename: Lucas P
authors.initials: LP
authors.lastname: Carvalho
authors.affiliation: Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT) (CNPq/MCT), Salvador, BA, Brazil.
authors.forename: Adriano
authors.initials: A
authors.lastname: Queiroz
authors.affiliation: Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT) (CNPq/MCT), Salvador, BA, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Machado
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Scott
authors.affiliation: Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT) (CNPq/MCT), Salvador, BA, Brazil.
authors.forename: Edgar M
authors.initials: EM
authors.lastname: Carvalho
authors.affiliation: Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT) (CNPq/MCT), Salvador, BA, Brazil olivinhaufba@gmail.com.
authors.forename: Olívia
authors.initials: O
authors.lastname: Bacellar
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D058070:Asymptomatic Diseases; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D002908:Chronic Disease; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053804:Granzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D007892:Leishmania braziliensis / Q000276:immunology / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D018655:Lymphocyte Count; D009000:Monocytes / Q000276:immunology / Q000469:parasitology; D061251:Primary Cell Culture; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000953:Antigens, Protozoan; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D007371:Interferon-gamma; D053804:Granzymes