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The thymus undergoes involution during childhood, and thymocyte and thymic epithelial cell (TEC) numbers decline. Given that adaptive immunity depends on T\u2010cells recognising diverse antigens via their unique T\u2010cell receptor (TCR), the precise age\u2010related changes in TCR repertoire composition are key to understand immunity. To investigate the influence of age on the thymic TCR repertoire we sequenced TCR\u03b1 and TCR\u03b2 transcripts from developmentally defined thymocyte populations from 4\u2010week, 12\u2010month and 18\u2010month\u2010old mice, and from thymocytes recovering from hydrocortisone\u2010treatment, and athymic recipients of RAG1\u2010deficient thymus transplants. The 18\u2010month thymus selected TCR repertoires with distinctive patterns of VxJ and CDR3 k\u2010mer usage compared to young thymus, indicating it had a qualitatively different repertoire with different specificity. It also selected a less diverse TCR\u03b2 repertoire with more expanded clones than young thymus. On recovery from hydrocortisone\u2010treatment, both 4\u2010week and 12\u2010month thymus showed bias towards foetal\u2010like 3\u2032TRAVx5\u2032TRAJ rearrangements, but 12\u2010month thymus also produced less diverse and evenly distributed TCR\u03b2 repertoires, with increased expansion of TCR\u03b2 clones at the CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    CD44\n                    <jats:sup>\u2212<\/jats:sup>\n                    intracellularTCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    stage, increased TRBJ\u20101\u2010cluster usage and distinctive patterns of combinatorial VxJ usage. Transplantation of athymic nude recipients with old RAG1\u2010deficient thymus generated less diverse, less evenly distributed TCR repertoires with different combinatorial VxJ usage than those generated by young transplants. Taken together our experiments show that the old thymus generates qualitatively different TCR repertoires than young thymus and the non\u2010lymphoid compartment of the thymus contributes strongly to these changes and to age\u2010associated decline in TCR repertoire diversity.\n                  <\/jats:p>","DOI":"10.1111\/acel.70675","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:41:08Z","timestamp":1787290868000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Thymic Microenvironment Shapes Age\u2010Related Qualitative Changes in the\n                    <scp>TCR<\/scp>\n                    Repertoire"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7040-8528","authenticated-orcid":false,"given":"Jasmine","family":"Rowell","sequence":"first","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health  London 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