title: Regulatory T cells phenotype in different clinical forms of Chagas' disease.
abstract: CD25(High) CD4+ regulatory T cells (Treg cells) have been described as key players in immune regulation, preventing infection-induced immune pathology and limiting collateral tissue damage caused by vigorous anti-parasite immune response. In this review, we summarize data obtained by the investigation of Treg cells in different clinical forms of Chagas' disease. Ex vivo immunophenotyping of whole blood, as well as after stimulation with Trypanosoma cruzi antigens, demonstrated that individuals in the indeterminate (IND) clinical form of the disease have a higher frequency of Treg cells, suggesting that an expansion of those cells could be beneficial, possibly by limiting strong cytotoxic activity and tissue damage. Additional analysis demonstrated an activated status of Treg cells based on low expression of CD62L and high expression of CD40L, CD69, and CD54 by cells from all chagasic patients after T. cruzi antigenic stimulation. Moreover, there was an increase in the frequency of the population of Foxp3+ CD25(High)CD4+ cells that was also IL-10+ in the IND group, whereas in the cardiac (CARD) group, there was an increase in the percentage of Foxp3+ CD25(High) CD4+ cells that expressed CTLA-4. These data suggest that IL-10 produced by Treg cells is effective in controlling disease development in IND patients. However, in CARD patients, the same regulatory mechanism, mediated by IL-10 and CTLA-4 expression is unlikely to be sufficient to control the progression of the disease. These data suggest that Treg cells may play an important role in controlling the immune response in Chagas' disease and the balance between regulatory and effector T cells may be important for the progression and development of the disease. Additional detailed analysis of the mechanisms on how these cells are activated and exert their function will certainly give insights for the rational design of procedure to achieve the appropriate balance between protection and pathology during parasite infections.
authors.affiliation: Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, Brasil.
authors.forename: Fernanda Fortes
authors.initials: FF
authors.lastname: de Araújo
authors.forename: Danielle Marquete
authors.initials: DM
authors.lastname: Vitelli-Avelar
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.forename: Paulo Renato
authors.initials: PR
authors.lastname: Antas
authors.forename: Juliana
authors.initials: J
authors.lastname: Assis Silva Gomes
authors.forename: Renato
authors.initials: R
authors.lastname: Sathler-Avelar
authors.forename: Manoel
authors.initials: M
authors.lastname: Otávio Costa Rocha
authors.forename: Silvana Maria
authors.initials: SM
authors.lastname: Elói-Santos
authors.forename: Rosa Teixeira
authors.initials: RT
authors.lastname: Pinho
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Correa-Oliveira
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D014355:Chagas Disease / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry* / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology
chemical_list: D015703:Antigens, CD