{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T14:28:46Z","timestamp":1775744926122,"version":"3.50.1"},"reference-count":76,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,4,8]]},"abstract":"<jats:p>CD4+Foxp3+ regulatory T cells (Treg cells) are largely autoreactive yet escape clonal deletion in the thymus. We demonstrate here that CD27\u2013CD70 co-stimulation in the thymus rescues developing Treg cells from apoptosis and thereby promotes Treg cell generation. Genetic ablation of CD27 or its ligand CD70 reduced Treg cell numbers in the thymus and peripheral lymphoid organs, whereas it did not alter conventional CD4+Foxp3\u2212 T cell numbers. The CD27\u2013CD70 pathway was not required for pre-Treg cell generation, Foxp3 induction, or mature Treg cell function. Rather, CD27 signaling enhanced positive selection of Treg cells within the thymus in a cell-intrinsic manner. CD27 signals promoted the survival of thymic Treg cells by inhibiting the mitochondrial apoptosis pathway. CD70 was expressed on Aire\u2212 and Aire+ medullary thymic epithelial cells (mTECs) and on dendritic cells (DCs) in the thymic medulla. CD70 on both mTECs and DCs contributed to Treg cell development as shown in BM chimera experiments with CD70-deficient mice. In vitro experiments indicated that CD70 on the CD8\u03b1+ subset of thymic DCs promoted Treg cell development. Our data suggest that mTECs and DCs form dedicated niches in the thymic medulla, in which CD27\u2013CD70 co-stimulation rescues developing Treg cells from apoptosis, subsequent to Foxp3 induction by TCR and CD28 signals.<\/jats:p>","DOI":"10.1084\/jem.20112061","type":"journal-article","created":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T21:10:07Z","timestamp":1364850607000},"page":"715-728","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":145,"title":["Epithelial and dendritic cells in the thymic medulla promote CD4+Foxp3+ regulatory T cell development via the CD27\u2013CD70 pathway"],"prefix":"10.1084","volume":"210","author":[{"given":"Jonathan M.","family":"Coquet","sequence":"first","affiliation":[{"name":"Division of Immunology 1 and 2"},{"name":"Division of Biological Stress Responses, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands 1 and 2"}]},{"given":"Julie C.","family":"Ribot","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal 3"}]},{"given":"Nikolina","family":"B\u0105ba\u0142a","sequence":"additional","affiliation":[{"name":"Division of Immunology 1 and 2"},{"name":"Division of Biological Stress Responses, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands 1 and 2"}]},{"given":"Sabine","family":"Middendorp","sequence":"additional","affiliation":[{"name":"Division of Immunology 1 and 2"},{"name":"Division of Biological Stress Responses, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands 1 and 2"}]},{"given":"Gerda","family":"van der Horst","sequence":"additional","affiliation":[{"name":"Division of Immunology 1 and 2"},{"name":"Division of Biological Stress Responses, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands 1 and 2"}]},{"given":"Yanling","family":"Xiao","sequence":"additional","affiliation":[{"name":"Division of Immunology 1 and 2"},{"name":"Division of Biological Stress Responses, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands 1 and 2"}]},{"given":"Joana F.","family":"Neves","sequence":"additional","affiliation":[{"name":"Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, England, UK 4"},{"name":"Programa Doutoral de Biologia Experimental e Biomedicina, Centro de Neuroci\u00eancias e Biologia Celular, Universidade de Coimbra, 3000-214 Coimbra, Portugal 5"}]},{"given":"Diogo","family":"Fonseca-Pereira","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal 3"}]},{"given":"Heinz","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Division of Immunology 1 and 2"},{"name":"Division of Biological Stress Responses, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands 1 and 2"}]},{"given":"Daniel J.","family":"Pennington","sequence":"additional","affiliation":[{"name":"Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, England, UK 4"}]},{"given":"Bruno","family":"Silva-Santos","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal 3"},{"name":"Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal 6"}]},{"given":"Jannie","family":"Borst","sequence":"additional","affiliation":[{"name":"Division of Immunology 1 and 2"},{"name":"Division of Biological Stress Responses, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands 1 and 2"}]}],"member":"291","published-online":{"date-parts":[[2013,4,1]]},"reference":[{"key":"2023072601403313100_bib1","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1038\/nri1248","article-title":"CD28-mediated co-stimulation: a quantitative support for TCR signalling","volume":"3","author":"Acuto","year":"2003","journal-title":"Nat. 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