Análise de células CD4+CD25+FoxP3+ no timo de camundongos infectados pelo Trypanosoma cruzi. / Analysis of cells CD4 CD25 FoxP3 in the thymus of mice infected for the Trypanosoma cruzi.

AUTOR(ES)

Flávia Calmon Hamaty

DATA DE PUBLICAÇÃO

2008

RESUMO

Natural regulatory T cells arise in the thymus during the normal process of differentiation and participate in the control of auto and alloimmune responses. Specifically in parasite infections, these cells may have antagonist roles, in favor of the microorganism or the host. Previous studies from our Laboratory revealed that acute Trypanosoma cruzi (T. cruzi) infection promotes several alterations in lymphoid organs, including the thymus. These alterations comprise the thymic microenvironment and developing thymocytes. Considering that the thymus is the generator of natural regulatory T cells and also a target for T. cruzi infection, we investigated the alterations in thymic T cells harboring the regulatory phenotype CD4+CD25+FoxP3+ during infection. We also analyzed this subpopulation in the spleen, subcutaneous and mesentheric lymph nodes. Our first observation was a progressive relative enrichment of T cells CD4+CD25+FoxP3+ in the thymus and mesentheric lymph nodes in acutely infected mice, although the severe atrophy of these organs revealed a decrease in absolute numbers of this cell subset. Additionally, there was a relative increase in this subpopulation in the spleen and decrease in subcutaneous lymph nodes, with increase in absolute cell numbers. Regarding the expression of extracellular matrix and chemokine receptors, we showed that thymic CD4+CD25+FoxP3+ T cells of infected animals express lower levels of VLA-4, VLA-5, VLA-6, CXCR4 and CCR7. Confocal microscopy observations suggest an increased interaction between FoxP3+ cells and the thymic microenvironment, including thymic epithelial cells, as well as with fibronectin and laminin, whose deposition is increased during infection. Our data suggest that T. cruzi acute infection affects the thymic generation and export of T CD4+CD25+FoxP3+ cells, possibly contributing to the pathogenesis of the disease.

ASSUNTO(S)

thymus gland antigens cd4 t-lymphocytes trypanosoma cruzi chagas disease trypanosoma cruzi subunidade alfa de receptor de interleucina-2 linfócitos t antígenos cd4 doença de chagas imunologia aplicada timo interleukin-2 receptor alpha subunit

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