{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:46:00Z","timestamp":1791287160216,"version":"4.1.0"},"reference-count":36,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6216","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2014,12,19]]},"abstract":"<jats:p>\n            Immunological tolerance to self requires naturally occurring regulatory T (T\n            <jats:sub>reg<\/jats:sub>\n            ) cells. Yet how they stably control autoimmune T cells remains obscure. Here, we show that T\n            <jats:sub>reg<\/jats:sub>\n            cells can render self-reactive human CD8\n            <jats:sup>+<\/jats:sup>\n            T cells anergic (i.e., hypoproliferative and cytokine hypoproducing upon antigen restimulation) in vitro, likely by controlling the costimulatory function of antigen-presenting cells. Anergic T cells were na\u00efve in phenotype, lower than activated T cells in T cell receptor affinity for cognate antigen, and expressed several coinhibitory molecules, including cytotoxic T lymphocyte\u2013associated antigen-4 (CTLA-4). Using these criteria, we detected in healthy individuals anergic T cells reactive with a skin antigen targeted in the autoimmune disease vitiligo. Collectively, our results suggest that T\n            <jats:sub>reg<\/jats:sub>\n            cell\u2013mediated induction of anergy in autoimmune T cells is important for maintaining self-tolerance.\n          <\/jats:p>","DOI":"10.1126\/science.aaa1292","type":"journal-article","created":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T08:12:06Z","timestamp":1418976726000},"page":"1536-1540","source":"Crossref","is-referenced-by-count":202,"title":["Detection of self-reactive CD8\n            <sup>+<\/sup>\n            T cells with an anergic phenotype in healthy individuals"],"prefix":"10.1126","volume":"346","author":[{"given":"Yuka","family":"Maeda","sequence":"first","affiliation":[{"name":"Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyoshi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danbee","family":"Ha","sequence":"additional","affiliation":[{"name":"Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Hamaguchi","sequence":"additional","affiliation":[{"name":"Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuro","family":"Saito","sequence":"additional","affiliation":[{"name":"Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Nishioka","sequence":"additional","affiliation":[{"name":"Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan."},{"name":"Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Wing","sequence":"additional","affiliation":[{"name":"Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Adeegbe","sequence":"additional","affiliation":[{"name":"Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Katayama","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1178"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.1.35"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.14.6458"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.6.1203"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.5.705"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.4049\/jimmunol.162.9.5317","article-title":"Thymus and autoimmunity: Production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance","volume":"162","author":"Itoh M.","year":"1999","unstructured":"Itoh M., Takahashi T., Sakaguchi N., Kuniyasu Y., Shimizu J., Otsuka F., Sakaguchi S., Thymus and autoimmunity: Production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. 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