{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T14:28:45Z","timestamp":1775744925538,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    \u03b3\u03b4T cells are produced in the thymus throughout life and provide immunity at epithelial\u2010rich sites. Unlike conventional \u03b1\u03b2T cells, \u03b3\u03b4T\u2010cell development involves intrathymic acquisition of effector function, with priming for either IL17 or IFN\u2010\u03b3 production occurring during embryonic or adult life, respectively. How the thymus controls effector\u2010primed \u03b3\u03b4T\u2010cell generation in adulthood is poorly understood. Here, we distinguished de novo \u03b3\u03b4T cells from those undergoing thymus recirculation and\/or retention using Rag2GFP mice alongside markers of maturation\/effector priming including CD24, CD25, CD73, and IFN\u2010\u03b3, the latter by crossing with IFN\u2010\u03b3\n                    <jats:sup>YFP<\/jats:sup>\n                    GREAT mice. We categorize newly developing \u03b3\u03b4T\u2010cells into an ordered sequence where CD25\n                    <jats:sup>+<\/jats:sup>\n                    CD73\n                    <jats:sup>\u2212<\/jats:sup>\n                    IFN\u2010\u03b3\n                    <jats:sup>YFP\u2212<\/jats:sup>\n                    precursors are followed sequentially by CD25\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD73\n                    <jats:sup>+<\/jats:sup>\n                    IFN\u2010\u03b3\n                    <jats:sup>YFP\u2212<\/jats:sup>\n                    intermediates and CD25\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD73\n                    <jats:sup>+<\/jats:sup>\n                    IFN\u2010\u03b3\n                    <jats:sup>YFP+<\/jats:sup>\n                    effectors. To determine intrathymic requirements controlling this sequence, we examined \u03b3\u03b4T\u2010cell development in\n                    <jats:italic>\n                      Relb\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    thymus grafts that lack medullary microenvironments. Interestingly, medulla deficiency did not alter CD25\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4T\u2010cell precursor generation, but significantly impaired development of effector primed stages. This impact on \u03b3\u03b4T\u2010cell priming was mirrored in\n                    <jats:italic>plt\/plt<\/jats:italic>\n                    mice lacking the medullary chemoattractants CCL19 and CCL21, and also\n                    <jats:italic>\n                      Ccl21a\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    but not\n                    <jats:italic>\n                      Ccl19\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Collectively, we identify the medulla as an important site for effector priming during adult \u03b3\u03b4T\u2010cell development and demonstrate a specific role for the medullary epithelial product CCL21 in this process.\n                  <\/jats:p>","DOI":"10.1002\/eji.202350388","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T21:58:05Z","timestamp":1679003885000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The medulla controls effector primed \u03b3\u03b4T\u2010cell development in the adult mouse thymus"],"prefix":"10.1002","volume":"53","author":[{"given":"Kieran D.","family":"James","sequence":"first","affiliation":[{"name":"Institute of Immunology and Immunotherapy University of Birmingham  Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea J.","family":"White","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy University of Birmingham  Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William E.","family":"Jenkinson","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy University of Birmingham  Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2917-4085","authenticated-orcid":false,"given":"Graham","family":"Anderson","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy University of Birmingham  Birmingham 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