Several T cell abnormalities have been described in the course of acute Trypanosoma cruzi infection in mice, including severe effects on the thymus. In the present study, looking at the expression of extracellular matrix ligands in the thymus, we observed that deposits of fibronectin and laminin increased progressively during the course of infection, reaching a maximum at the peak of parasitemia and thymic atrophy. Concomitantly, membrane expression of fibronectin and laminin receptors (VLA-4, VLA-5 and VLA-6) was also enhanced on thymocyte subsets of infected mice. These results correlated with changes in intrathymic thymocyte migration ability during the acute phase of infection, when a higher fibronectindependent transmigratory activity of CD4 + CD8 + thymocytes was observed. Strikingly, we detected higher frequency of immature and high VLA-expressing CD4 + CD8 + T cells in the peripheral lymphoid organs of infected mice at the peak of parasitemia. These cells seemed to be thymus dependent, since significantly lower amounts of them were found in thymectomized mice, and some of them carry "prohibited" V g segments of the TCR. Our data suggest an imbalance in the intrathymic cell trafficking following acute T. cruzi infection, likely due to dysregulated extracellular matrix-dependent interactions.

Triiodothyronine (T3) exerts several effects on thymus physiology. In this sense, T3 is known to stimulate thymic microenvironmental cells to enhance the production of extracellular matrix (ECM) moieties, which are relevant in thymocyte migration. Here, we further investigated the in vivo influence of T3 on ECM production, as well as on ECM‐related T‐cell migration events. For this, BALB/c mice were subjected to two protocols of T3 treatment: long‐term (30 days) i.p. daily T3 injections or short‐term (16 h) after a single T3 intrathymic injection. These two treatments did promote an enhancement in the expression of fibronectin and laminin, in both cortex and medullary regions of the thymic lobules. As revealed by the long‐term treatment, the expression of ECM protein receptors, including VLA‐4, VLA‐5 and VLA‐6, was also increased in thymocyte subsets issued from T3‐treated mice. We further used thymic nurse cells (TNC) as an in vitro system to study the ECM‐related migration of immature thymocytes in the context of thymic epithelial cells. Even a single intrathymic injection of T3 resulted in an increase in the ex vivo exit of thymocytes from TNC lymphoepithelial complexes. Accordingly, when we evaluated thymocyte migration in transwell chambers pre‐coated with ECM proteins, we found an increase in the numbers of migrating cells, when thymocytes were derived from T3‐treated mice. Overall, our data show that in vivo intrathymic short‐term i.p. long‐term T3 treatments are able to modulate thymocyte migration, probably via ECM‐mediated interactions.