Estudo da apoptose como mecanismo de supressão induzido por células T reguladoras CD4+CD25 high FOXP3+ de pacientes nas diferentes formas clínicas da doença de Chagas

Abstract

The regulatory T cells CD4+CD25highFOXP3+ (Treg) were described as cells with the capacity to control the immune response through the supression of antigen presenting cells and effector T cells. Many mechanisms induced by these cells have been proposed in the T. cruzi infection, as apoptosis and cytokines secretion. However, the role of Treg cells in human Chagas disease is not stablished yet. Then, the aim of this study was to evaluate the expression of apoptotic molecules in regulatory T cells CD4+CD25highFOXP3+ of patients with the clinical forms IND and CARD (CCCV). Thereunto, peripheral blood samples of patients with indeterminate form (IND) and cardiac form (CARD) were collected. Posteriorly, we evaluate the frequency of T cells CD4+CD25highFOXP3+, as well as the expression of the following surface and intracitoplasmic molecules: CD39, CD95, CD95L, PD1, PD-1L e IL-17. Peripheral blood samples of non-infected individuals (NI) were used as control. The results confirmed the higher frequency of T cells CD4+CD25highFOXP3+ in patients of IND group than CARD and NI groups. The evaluation of CD39 and CD95L expression by Treg cells, showed higher expression of those molecules in patients of IND group than patients of CARD or NI groups. However, Treg cells of CARD patients presented higher mean intensity of fluorescence related to CD95 expression than Treg of IND or NI patients. We observed positive correlation in the expression of both PD1 and PD1-L in the surface of Treg of CARD patients. The results also showed higher frequency of T cells CD4+CD25highFOXP3+IL-17+ in patients of the IND group. After all, we identified monocytes as the main cells that undergo apoptosis in the different studied groups. In conclusion, the secretion of IL-17 is probably important in the development of chronic phase of Chagas disease. Moreover, the differential expression of each apoptosis-inducing molecule and their receptors suggest that distinct mechanisms may be presented in each clinical form of Chagas disease.