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10.1073/pnas.1519118112 http://scihub22266oqcxt.onion/10.1073/pnas.1519118112 C4640754!4640754 !26483497     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26483497 &cmd=llinks): Failed to open stream: HTTP request failed! 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Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus |pdf=|usr=}}{{26483497 }} gab.com Text Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=26483497 #FOAvip The fate and numbers of hematopoietic stem cells (HSC) and their progeny that seed the thymus constitute a fundamental question with important clinical implications. HSC transplantation is often complicated by limited T-cell reconstitution, especially when HSC from umbilical cord blood are used. Attempts to improve immune reconstitution have until now been unsuccessful, underscoring the need for better insight into thymic reconstitution. Here we made use of the NOD-SCID-IL-2R?(-/-) xenograft model and lentiviral cellular barcoding of human HSCs to study T-cell development in the thymus at a clonal level. Barcoded HSCs showed robust (>80% human chimerism) and reproducible myeloid and lymphoid engraftment, with T cells arising 12 wk after transplantation. A very limited number of HSC clones (<10) repopulated the xenografted thymus, with further restriction of the number of clones during subsequent development. Nevertheless, T-cell receptor rearrangements were polyclonal and showed a diverse repertoire, demonstrating that a multitude of T-lymphocyte clones can develop from a single HSC clone. Our data imply that intrathymic clonal fitness is important during T-cell development. As a consequence, immune incompetence after HSC transplantation is not related to the transplantation of limited numbers of HSC but to intrathymic events. Twit Text FOAVip Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=26483497 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26483497 #FOAvip English Wikipedia <ref>{{Cite pmid|26483497 }}</ref> Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus #MMPMID26483497 Brugman MH ; Wiekmeijer AS ; van Eggermond M ; Wolvers-Tettero I ; Langerak AW ; de Haas EF ; Bystrykh LV ; van Rood JJ ; de Haan G ; Fibbe WE ; Staal FJ Proc Natl Acad Sci U S A 2015[Nov]; 112 (44 ): E6020-7 PMID26483497 show ga The fate and numbers of hematopoietic stem cells (HSC) and their progeny that seed the thymus constitute a fundamental question with important clinical implications. HSC transplantation is often complicated by limited T-cell reconstitution, especially when HSC from umbilical cord blood are used. Attempts to improve immune reconstitution have until now been unsuccessful, underscoring the need for better insight into thymic reconstitution. Here we made use of the NOD-SCID-IL-2R?(-/-) xenograft model and lentiviral cellular barcoding of human HSCs to study T-cell development in the thymus at a clonal level. Barcoded HSCs showed robust (>80% human chimerism) and reproducible myeloid and lymphoid engraftment, with T cells arising 12 wk after transplantation. A very limited number of HSC clones (<10) repopulated the xenografted thymus, with further restriction of the number of clones during subsequent development. Nevertheless, T-cell receptor rearrangements were polyclonal and showed a diverse repertoire, demonstrating that a multitude of T-lymphocyte clones can develop from a single HSC clone. Our data imply that intrathymic clonal fitness is important during T-cell development. As a consequence, immune incompetence after HSC transplantation is not related to the transplantation of limited numbers of HSC but to intrathymic events. |Animals [MESH] |Bone Marrow Cells/*cytology [MESH] |Humans [MESH] |Mice [MESH] |Mice, Inbred NOD [MESH] |Mice, SCID [MESH] |T-Lymphocytes/*cytology [MESH]Development of a diverse human T-cell repertoire despite stringent res(epmc).pdf DeepDyve Pubget Overpricing