Analysis of cells CD4 CD25 FoxP3 in the thymus of mice infected for the Trypanosoma cruzi.
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 antagonistroles, 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 alterationscomprise the thymic microenvironment and developing thymocytes. Considering that the thymus is the generator of natural regulatory T cells and also a targetfor T. cruzi infection, we investigated the alterations in thymic T cells harboring the regulatory phenotype CD4+CD25+FoxP3+ during infection. We also analyzedthis subpopulation in the spleen, subcutaneous and mesentheric lymph nodes. Our first observation was a progressive relative enrichment of T cellsCD4+CD25+FoxP3+ in the thymus and mesentheric lymph nodes in acutely infected mice, although the severe atrophy of these organs revealed a decreasein 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 expressionof 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 suggestan increased interaction between FoxP3+ cells and the thymicmicroenvironment, 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 TCD4+CD25+FoxP3+ cells, possibly contributing to the pathogenesis of the disease.
Advisor:Suse Dayse Silva Barbosa; Wilson Savino
School:Faculdades Oswaldo Cruz
Source Type:Master's Thesis
Keywords:Trypanosoma cruzi T-Lymphocytes Thymus Gland Chagas Disease Antigens CD4
Date of Publication:03/13/2008