{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:17:02Z","timestamp":1785417422661,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,17]]},"group-title":"Immunology","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["RG-2111-38681 (to D.H.)"],"award-info":[{"award-number":["RG-2111-38681 (to D.H.)"]}],"id":[{"id":"https:\/\/ror.org\/03019wv17","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Faculty Career Development Award (to D. H.)"],"award-info":[{"award-number":["Faculty Career Development Award (to D. H.)"]}],"id":[{"id":"https:\/\/ror.org\/04b6nzv94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32GM007057-47 (to X.L.)"],"award-info":[{"award-number":["T32GM007057-47 (to X.L.)"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Here we identify NKG2C\n                  <jats:sup>+<\/jats:sup>\n                  CD27\n                  <jats:sup>\u2212<\/jats:sup>\n                  as a novel surface marker unifying multiple previously reported CD8\n                  <jats:sup>+<\/jats:sup>\n                  regulatory T cell (Treg) populations. This population displays high clonality and divides into CD226\n                  <jats:sup>\u2212<\/jats:sup>\n                  (Treg1) and CD226\n                  <jats:sup>+<\/jats:sup>\n                  (Treg2) subsets, with Treg2 exhibiting stronger suppressive activities. Up to 35% of CD8\n                  <jats:sup>+<\/jats:sup>\n                  T\n                  <jats:sub>EMRA<\/jats:sub>\n                  cells are Tregs, whereas approximately 85% of CD8\n                  <jats:sup>+<\/jats:sup>\n                  Tregs are T\n                  <jats:sub>EMRA<\/jats:sub>\n                  cells, which increase with aging. These findings establish a unified and novel cell surface marker for CD8\n                  <jats:sup>+<\/jats:sup>\n                  Tregs and their subsets, which resolves prior heterogeneity in the field, and show that CD8\n                  <jats:sup>+<\/jats:sup>\n                  T\n                  <jats:sub>EMRA<\/jats:sub>\n                  cells are a heterogeneous population that includes T cells with regulatory function. Our findings provide a critical framework for the isolation and in-depth functional characterization of CD8\n                  <jats:sup>+<\/jats:sup>\n                  Tregs in health, aging, and disease.\n                <\/jats:p>","DOI":"10.64898\/2026.06.15.732401","type":"posted-content","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T20:45:15Z","timestamp":1781729115000},"source":"Crossref","is-referenced-by-count":0,"title":["NKG2C\n                  <sup>+<\/sup>\n                  CD27\n                  <sup>\u2212<\/sup>\n                  Defines Human CD8\n                  <sup>+<\/sup>\n                  Regulatory T Cells"],"prefix":"10.64898","author":[{"given":"Xuyang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somen K.","family":"Mistri","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Harvard Medical School and Mass General Brigham, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Cao","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Harvard Medical School and Mass General Brigham, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh K.","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Harvard Medical School and Mass General Brigham, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hemberg","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Harvard Medical School and Mass General Brigham, Boston, MA 02115, USA"},{"name":"Gene Lay Institute for Immunology and Inflammation, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard L.","family":"Weiner","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Harvard Medical School and Mass General Brigham, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Hu","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Harvard Medical School and Mass General Brigham, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026061906050628000_2026.06.15.732401v1.1","first-page":"723","article-title":"Cell interactions in the induction of tolerance: the role of thymic lymphocytes","volume":"18","year":"1970","journal-title":"Immunology"},{"key":"2026061906050628000_2026.06.15.732401v1.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.01.040183.002255"},{"key":"2026061906050628000_2026.06.15.732401v1.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.18.5704"},{"key":"2026061906050628000_2026.06.15.732401v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/ni0404-347"},{"key":"2026061906050628000_2026.06.15.732401v1.5","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.3.1151"},{"key":"2026061906050628000_2026.06.15.732401v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/83784"},{"key":"2026061906050628000_2026.06.15.732401v1.7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200320274"},{"key":"2026061906050628000_2026.06.15.732401v1.8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.708874"},{"key":"2026061906050628000_2026.06.15.732401v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2025.02.010"},{"key":"2026061906050628000_2026.06.15.732401v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/ni1063"},{"key":"2026061906050628000_2026.06.15.732401v1.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.8.4533"},{"key":"2026061906050628000_2026.06.15.732401v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(95)80079-4"},{"key":"2026061906050628000_2026.06.15.732401v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/ni0504-469"},{"key":"2026061906050628000_2026.06.15.732401v1.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018974108"},{"key":"2026061906050628000_2026.06.15.732401v1.15","doi-asserted-by":"crossref","unstructured":"M. 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