{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T22:27:53Z","timestamp":1769207273742,"version":"3.49.0"},"reference-count":76,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"4","funder":[{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["2405-06956"],"award-info":[{"award-number":["2405-06956"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wanek Family Foundation to Cure Type Diabetes Innovative","award":["CY-2021"],"award-info":[{"award-number":["CY-2021"]}]},{"name":"Margie and Robert Petersen Foundation","award":["2009998"],"award-info":[{"award-number":["2009998"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,1,23]]},"abstract":"<jats:p>\n                    CUB domain\u2013containing protein 1 (CDCP1; CD318) is a surface glycoprotein known as a ligand for CD6, primarily studied in tumor immunology where it associates with poor prognosis. CD318 is expressed in myeloid dendritic cells and activated monocytes associated with immunoregulatory functions. Here, selective expression of CD318 on a subset of activated human CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, but not CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, is shown, defining suppressor function of this cell population. CD318\n                    <jats:sup>+<\/jats:sup>\n                    CD8 T cells exhibited reduced PD-1 and KLRG-1 expression, diminished interferon-\u03b3 and tumor necrosis factor\u2013\u03b1 production, and potent suppression of autologous CD4 and CD8 T cell activation in vitro. Notably, CD8 T cells from patients with type 1 diabetes (T1D) showed reduced CD318 induction compared with controls. Mechanistically, CD318 inhibited T cell receptor signaling independently of SHP2, while its induction required interleukin-2\u2013dependent mTOR activation. These findings identify CD318 as a marker of human CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells with implications for immune regulation and autoimmunity.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adz4203","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T18:58:41Z","timestamp":1769194721000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["CD318 expression defines a novel subset of human CD8\n                    <sup>+<\/sup>\n                    regulatory T cells"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2375-2585","authenticated-orcid":true,"given":"Jeong-su","family":"Do","sequence":"first","affiliation":[{"name":"Department of Immunology and Theranostics, City of Hope, Duarte, CA, USA."},{"name":"Beckman Research Institute and Arthur Riggs Diabetes &amp; Metabolism Research Institute, City of Hope, Duarte, CA, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8392-1707","authenticated-orcid":true,"given":"Wei-Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Theranostics, City of Hope, Duarte, CA, USA."},{"name":"Beckman Research Institute and Arthur Riggs Diabetes &amp; Metabolism Research Institute, City of Hope, Duarte, CA, USA."},{"name":"Irell &amp; Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA, USA."}]},{"given":"Yu-Wen","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Immunology and Theranostics, City of Hope, Duarte, CA, USA."},{"name":"Beckman Research Institute and Arthur Riggs Diabetes &amp; Metabolism Research Institute, City of Hope, Duarte, CA, USA."}]},{"given":"David","family":"Arribas-Layton","sequence":"additional","affiliation":[{"name":"Department of Immunology and Theranostics, City of Hope, Duarte, CA, USA."},{"name":"Beckman Research Institute and Arthur Riggs Diabetes &amp; Metabolism Research Institute, City of Hope, Duarte, CA, USA."}]},{"given":"Congcong","family":"Lu","sequence":"additional","affiliation":[{"name":"Beckman Research Institute and Arthur Riggs Diabetes &amp; Metabolism Research Institute, City of Hope, Duarte, CA, USA."},{"name":"Department of Translational Research and Cellular Therapeutics, City of Hope, Duarte, CA, USA."}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7093-3918","authenticated-orcid":true,"given":"Angel","family":"Gu","sequence":"additional","affiliation":[{"name":"Beckman Research Institute and Arthur Riggs Diabetes &amp; Metabolism Research Institute, City of Hope, Duarte, CA, USA."},{"name":"Department of Translational Research and Cellular Therapeutics, City of Hope, Duarte, CA, USA."}]},{"given":"Enrique","family":"Montero","sequence":"additional","affiliation":[{"name":"Beckman Research Institute and Arthur Riggs Diabetes &amp; Metabolism Research Institute, City of Hope, Duarte, CA, USA."}]},{"given":"Alexandre M.","family":"Carmo","sequence":"additional","affiliation":[{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular, Porto, Portugal."},{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9386-3918","authenticated-orcid":true,"given":"Helena","family":"Reijonen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Theranostics, City of Hope, Duarte, CA, USA."},{"name":"Beckman Research Institute and Arthur Riggs Diabetes &amp; Metabolism Research Institute, City of Hope, Duarte, CA, USA."},{"name":"Irell &amp; Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA, USA."}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.127.3.987"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000322720"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.004523"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389450117666160201105934"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-018-0089-9"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.12.004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.145662"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-013-0027-4"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02994"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.05.064"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01658-y"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1551"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI147334"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szad012"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704008114"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiad124"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.198"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.22-3-334"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.157038"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01864-24"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040528"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2024.103228"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02702"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2001406"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.256.5060.1213"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1467-x"},{"key":"e_1_3_2_28_2","first-page":"165.17","article-title":"Human KIR+ CD8+ T cells target pathogenic T cells in celiac disease and are active in autoimmune diseases and COVID-19","volume":"208","author":"Li J.","year":"2022","unstructured":"J. Li, M. Zaslavsky, Y. Su, J. Guo, M. J. Sikora, V. van Unen, A. Christophersen, S. H. Chiou, L. Chen, J. Li, X. Ji, J. Wilhelmy, A. M. McSween, B. A. Palanski, V. V. A. Mallajosyula, N. A. Bracey, G. K. R. Dhondalay, K. Bhamidipati, J. Pai, L. B. Kipp, J. E. Dunn, S. L. Hauser, J. R. Oksenberg, A. T. Satpathy, W. H. Robinson, C. L. Dekker, L. M. Steinmetz, C. Khosla, P. J. Utz, L. M. Sollid, Y. H. Chien, J. R. Heath, N. Q. Fernandez-Becker, K. C. Nadeau, N. Saligrama, M. M. Davis, Human KIR+ CD8+ T cells target pathogenic T cells in celiac disease and are active in autoimmune diseases and COVID-19. 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Gao, Y. Gao, Z. Li, Z. Chen, D. Lu, A. Tsun, B. Li, Synergy between IL-6 and TGF-\u03b2 signaling promotes FOXP3 degradation. Int. J. Clin. Exp. Pathol. 5, 626\u2013633 (2012).","journal-title":"Int. J. Clin. Exp. 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