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Publication : Thymus-autonomous T cell development in the absence of progenitor import.

First Author  Martins VC Year  2012
Journal  J Exp Med Volume  209
Issue  8 Pages  1409-17
PubMed ID  22778389 Mgi Jnum  J:189166
Mgi Id  MGI:5444564 Doi  10.1084/jem.20120846
Citation  Martins VC, et al. (2012) Thymus-autonomous T cell development in the absence of progenitor import. J Exp Med 209(8):1409-17
abstractText  Thymus function is thought to depend on a steady supply of T cell progenitors from the bone marrow. The notion that the thymus lacks progenitors with self-renewal capacity is based on thymus transplantation experiments in which host-derived thymocytes replaced thymus-resident cells within 4 wk. Thymus grafting into T cell-deficient mice resulted in a wave of T cell export from the thymus, followed by colonization of the thymus by host-derived progenitors, and cessation of T cell development. Compound Rag2(-/-)gamma(c)(-/-)Kit(W/Wv) mutants lack competitive hematopoietic stem cells (HSCs) and are devoid of T cell progenitors. In this study, using this strain as recipients for wild-type thymus grafts, we noticed thymus-autonomous T cell development lasting several months. However, we found no evidence for export of donor HSCs from thymus to bone marrow. A diverse T cell antigen receptor repertoire in progenitor-deprived thymus grafts implied that many thymocytes were capable of self-renewal. Although the process was most efficient in Rag2(-/-)gamma(c)(-/-)Kit(W/Wv) hosts, gamma(c)-mediated signals alone played a key role in the competition between thymus-resident and bone marrow-derived progenitors. Hence, the turnover of each generation of thymocytes is not only based on short life span but is also driven via expulsion of resident thymocytes by fresh progenitors entering the thymus.
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