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T cell development is under tight control of the thymic microenvironment. In turn, the integrity of the thymic microenvironment depends on the physical presence of developing T lymphocytes, a phenomenon designated "thymic crosstalk". We previously reported, using a novel mouse strain which has defects in both the thymic medina and cortex, that the induction of thymic cortex by bone marrow (BM) or fetal liver-derived T cell progenitors could be achieved on day 16 or 17 of gestation, but could not be induced in adulthood. Here, we further define the time window for this induction by prothymocytes. We first show that the induction of thymic cortex can be achieved during the neonatal stage. In 2 to 4 day post-partal neonates, BM injection could fully reconstituted the thymic structure and T cell compartments. Mice more than 4 days old showed decreased susceptibility to reconstitution. After 8 days, the susceptibility diminished. Next, we tested whether the induction could be obtained by prothymocytes derived from RAG-/- BM. Neonates injected with RAG-/- BM were found to have a normal thymic cortex. Moreover, these RAG-/- BM-injected neonates could be further reconstituted by wildtype BM at adulthood, leading to a wild-type thymus. In contrast, mice injected with RAG-/- BM in adulthood did not have a normal thymic cortex. Taken together, we defined a window for the induction of thymic cortex, and demonstrate that prothymocytes derived from RAG-/- mice are capable of induction within that window.


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