{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T05:13:10Z","timestamp":1772255590986,"version":"3.50.1"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2010,10,1]],"date-time":"2010-10-01T00:00:00Z","timestamp":1285891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thymocytes differentiate into CD4+ Foxp3+ regulatory T cells (TR) upon interaction between their TCR and peptide\u2013MHC II complexes locally expressed in the thymus. Conversion of naive CD4+ T cells into TR can additionally take place in the periphery under noninflammatory conditions of Ag encounter. In this study, making use of TCR transgenic models naturally devoid of Foxp3+ cells, we report de novo generation of TR upon a single footpad injection of Ag mixed with a classic proinflammatory adjuvant. Abrupt TR differentiation upon immunization occurred intrathymically and was essential for robust tolerance induction in a mouse model of spontaneous encephalomyelitis. This phenomenon could be attributed to a specific feature of thymocytes, which, in contrast to mature peripheral CD4+ T cells, were insensitive to the inhibitory effects of IL-6 on the induction of Foxp3 expression. Our findings uncover a pathway for TR generation with major implications for immunity and tolerance induction.<\/jats:p>","DOI":"10.4049\/jimmunol.1001281","type":"journal-article","created":{"date-parts":[[2010,9,3]],"date-time":"2010-09-03T23:05:04Z","timestamp":1283555104000},"page":"3829-3833","source":"Crossref","is-referenced-by-count":15,"title":["Cutting Edge: Intrathymic Differentiation of Adaptive Foxp3+ Regulatory T Cells upon Peripheral Proinflammatory Immunization"],"prefix":"10.1093","volume":"185","author":[{"given":"Santiago","family":"Zelenay","sequence":"first","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , Oeiras ,","place":["Portugal"]}]},{"given":"Marie-Louise","family":"Bergman","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , Oeiras ,","place":["Portugal"]}]},{"given":"Ricardo Sousa","family":"Paiva","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , Oeiras ,","place":["Portugal"]}]},{"given":"Andreia C","family":"Lino","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , Oeiras ,","place":["Portugal"]}]},{"given":"Ana C","family":"Martins","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , Oeiras ,","place":["Portugal"]}]},{"given":"Jo\u00e3o H","family":"Duarte","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , Oeiras ,","place":["Portugal"]}]},{"given":"Maria F","family":"Moraes-Fontes","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , Oeiras ,","place":["Portugal"]}]},{"given":"Angelina M","family":"Bilate","sequence":"additional","affiliation":[{"name":"Molecular Pathogenesis Program, Skirball Institute for Biomolecular Medicine, New York University School of Medicine , New York, NY 10016"}]},{"given":"Juan J","family":"Lafaille","sequence":"additional","affiliation":[{"name":"Molecular Pathogenesis Program, Skirball Institute for Biomolecular Medicine, New York University School of Medicine , New York, NY 10016"}]},{"given":"Jocelyne","family":"Demengeot","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , Oeiras ,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2010,10,1]]},"reference":[{"key":"2025032411574400800_r1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nri1085","article-title":"Negative selection\u2014clearing out the bad apples from the T-cell repertoire","volume":"3","author":"Palmer","year":"2003","journal-title":"Nat. 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