| Box 2. Thymic atrophy and negative selection in experimental acute Chagas disease. |
| It is largely established that interactions between TEC and thymocytes control the development of |
| the thymic microenvironment and T-cell development. Furthermore, many tissue-specific self- |
| proteins are known to be synthesized by medullary thymic epithelial cells (mTEC) that express |
| Aire. For this reason, Aire-expressing mTEC have a central role in the deletion of self-reactive |
| thymocytes during the process of negative selection [58–61]. In T. cruzi infection we showed that |
| the expression of Aire and highly selective tissue restricted antigens was readily detectable in |
| whole thymus by real-time PCR analysis from infected mice, suggesting an expression of peripheral |
| antigens which would be sufficient to modulate the tolerance induction by the negative selection |
| process [62]. |
| During the acute phase of infection, as the thymic atrophy becomes evident, there is an increase |
| in numbers of apoptotic intrathymic DP cells, compared to their respective normal counterparts. |
| Although this phenomenon may be a consequence of the changes observed in the organ, our data |
| show that along the DP depletion there is sustained expression of Bim, a proapoptotic factor |
| essential for thymocyte negative selection. Further analysis, by using an OTII TCR transgenic |
| system, revealed that the administration of the cognate OVA peptide in the acutely infected mice |
| undergoing thymic atrophy can induce TCR-stimulation-induced apoptosis of semimature |
| thymocytes. These data point out that negative selection operates normally during infection- |
| promoted thymic atrophy, since the DP cells can be negatively selected in the infected thymus by |
| antigen-induced depletion [62]. |
