title: Role of costimulatory molecules in immune response of patients with cutaneous leishmaniasis.
abstract: T cell-mediated immunity is critical in resistance against Leishmania parasites, and T cell activation requires signals provided by costimulatory molecules. Herein we evaluated the role of costimulatory molecules on cytokine production and T cell surface molecule expression by peripheral blood mononuclear cells (PBMC) from cutaneous leishmaniasis (CL) patients. PBMC from CL patients were stimulated with soluble Leishmania antigen (SLA, 10 microg/ml), in the presence or absence of soluble CTLA4-Ig to block CD28-B7 interaction or in the presence or absence of anti-human CD40L to block CD40-CD40L interaction. Supernatants were harvested to evaluate tumor necrosis factor alpha (TNF-alpha), interleukin 10 (IL-10), transforming growth factor beta (TGF-beta) and interferon gamma (IFN-gamma) production by ELISA. Cells were harvested after 48 h of culture, stained for specific activation markers and analyzed by flow cytometry. Results show that the blockade of CD28-B7 interaction by CTLA4-Ig downmodulated IFN-gamma, IL-10, and TNF-alpha secretion by PBMC from CL patients. No alteration was detected on either TGF-beta production or the expression of CTLA44 or CD25 on CD4+ and CD8+ T cells. When the CD40-CD40L interaction was blockade using anti-CD40L, we did not observe changes in cytokine production or in surface molecule expression. The blockade of the CD28-B7 interactions by CTLA4-Ig also did not alter cytokine production in volunteers immunized against tetanus toxoid (TT). Taken together, these data suggest that the interaction of CTLA4 and CD28-B7 is a TGF-beta-independent mechanism that specifically downmodulates the immune response in cutaneous leishmaniasis patients.
authors.affiliation: Laboratório de Imunoparasitologia, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Salvador, Bahia 40295-001, Brazil.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Favali
authors.forename: Dirceu
authors.initials: D
authors.lastname: Costa
authors.forename: Lilian
authors.initials: L
authors.lastname: Afonso
authors.forename: Viviane
authors.initials: V
authors.lastname: Conceição
authors.forename: Andréa
authors.initials: A
authors.lastname: Rosato
authors.forename: Fabiano
authors.initials: F
authors.lastname: Oliveira
authors.forename: Jackson
authors.initials: J
authors.lastname: Costa
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.forename: Claudia Ida
authors.initials: CI
authors.lastname: Brodskyn
mesh_terms: D000069594:Abatacept; D000328:Adult; D018106:CD28 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D016773:Leishmaniasis, Cutaneous / Q000097:blood / Q000276:immunology*; D007963:Leukocytes, Mononuclear; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018106:CD28 Antigens; D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000069594:Abatacept; D007371:Interferon-gamma