Experimental Trypanosoma cruzi infection alters the shaping of the central and peripheral T-cell repertoire

Abstract

We investigated the thymic and peripheral T-lymphocyte subsets in BALB/c mice undergoing acute or chronic Trypanosoma cruzi infection, in terms of expression of particular Vβ rearrangements of the T-cell receptor. We first confirmed the severe depletion of CD4 +CD8 + thymocytes following acute T. cruzi infection. By contrast, the numbers of CD4 +CD8 + cells in subcutaneous lymph nodes increased up to 16 times. In subcutaneous lymph nodes, we found CD4 +CD8 + cells that expressed prohibited segments TCRVβ5 and TCRVβ12 (which are physiologically deleted in the thymus of BALB/c mice), as did some mature single-positive cells (CD4 +CD8 – and CD4 –CD8 +). In the thymus of infected animals, although higher numbers of immature cells bearing such Vβ segments were seen, they were no longer detected in the mature single-positive stage, suggesting that negative selection occurs normally. We also found increased numbers of cells bearing the potentially autoreactive phenotype TCRVβ5 + and TCRVβ12 + in T-lymphocyte subsets from subcutaneous lymph nodes of T. cruzi chronically infected mice. In conclusion, our data indicate that immature T lymphocytes bearing prohibited TCRVβ segments leave the thymus and gain the lymph nodes, where they further differentiate into mature CD4 + or CD8 + cells. Conjointly, these findings show changes in the shaping of the central and peripheral T-cell repertoire in both acute and chronic phases of murine T. cruzi infection. The release of potentially autoreactive T cells in the periphery of the immune system may contribute to the autoimmune process found in both murine and human Chagas’ disease.