Imunoregulação na doença de Chagas humana: estudo das células T CD4- CD8- e mecanismos de controle de expressão de citocinas

• Ano de defesa: 2010
• Autor(a) principal: Fernanda Nobre Amaral
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Biologia Celular; Biologia celular; Chagas, Doença de; Células T Duplo negativas; Células T CD8 Negativas; Células T CD4 Negativas; Citocinas
• Link de acesso: http://hdl.handle.net/1843/BUOS-8RCNU3

Several studies have evaluated the involvement of CD4- CD8- T cells (double negatives DN) expressing alpha-beta TCR (TCRáâ) or gamma-delta (TCRãä) in the development of immune response against different parasites. These studies suggested that distinct subpopulations of DN T cells tend to have very different immune profiles, which can drive to a protective or pathogenic immune response. Thus, it is important to know if these cells have distinct roles in human Chagas disease. Besides evaluating the characteristics of different lymphocytes populations, it is also relevant to understand the expression profile of transcription factors linked to cytokines intracellular signaling which activates these cell; likewise, it is important to comprehend the gene regulation pathways involved with these cytokines. The main aim of this work was to evaluate the possible contributions of different DN T cell subpopulations; and the contribution of transcription factors and post-transcriptional regulators of cytokines on the immune response during T. cruzi infection. Our results showed that T. cruzi in vitro infection leads to DN Tcells expansion in patients with indeterminate (I) and dilated cardiac (DC) form. We have also observed that both subpopulations (áâ+ and ãä+) show a more activated profile, as they had a higher expression of CD69 in patients, when compared with control individuals. Only ãä+ subpopulation shows higher expression of granzyme A, after stimulus in DC patients. However, despite áâ DN T cells being more engaged in the production of pro-inflammatory cytokines, ãä DN T cells show a significant increase of antigen-specific IL-10 in group I whether compared to DC. The greater frequency of IL-10+ ãä DN T cells is correlated to the better prognostic of cardiac function clinical parameters. We have also seen that the presentation of lipid/glycolipid antigen via CD1 seems to be relevant in patients. Concerning transcription factors, DC lymphocytes showed a more inflammatory profile, observed through the increase of NFêB/STAT3 ratio after T. cruzi infection. As for IL-10 regulation, we observed lesser expression of miR106a after in vitro stimulus in I patients cells. These data, altogether, show distinct functional characteristics for áâ and ãä DN T cells related to distinct clinical profiles in human Chagas disease, and distinct pre and post-transcricional responses in I and DC