{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:50:34Z","timestamp":1792702234624,"version":"4.5.0"},"reference-count":65,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"85","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2023,7,28]]},"abstract":"<jats:p>\n                    Immune checkpoint inhibitor (ICI) therapies used to treat cancer, such as anti\u2013PD-1 antibodies, can induce autoimmune conditions in some individuals. The T cell mechanisms mediating such iatrogenic autoimmunity and their overlap with spontaneous autoimmune diseases remain unclear. Here, we compared T cells from the joints of 20 patients with an inflammatory arthritis induced by ICI therapy (ICI-arthritis) with two archetypal autoimmune arthritides, rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Single-cell transcriptomic and antigen receptor repertoire analyses highlighted clonal expansion of an activated effector CD8 T cell population in the joints and blood of patients with ICI-arthritis. These cells were identified as CD38\n                    <jats:sup>hi<\/jats:sup>\n                    CD127\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8 T cells and were uniquely enriched in ICI-arthritis joints compared with RA and PsA and also displayed an elevated interferon signature. In vitro, type I interferon induced CD8 T cells to acquire the ICI-associated CD38\n                    <jats:sup>hi<\/jats:sup>\n                    phenotype and enhanced cytotoxic function. In a cohort of patients with advanced melanoma, ICI therapy markedly expanded circulating CD38\n                    <jats:sup>hi<\/jats:sup>\n                    CD127\n                    <jats:sup>\u2212<\/jats:sup>\n                    T cells, which were frequently bound by the therapeutic anti\u2013PD-1 drug. In patients with ICI-arthritis, drug-bound CD8 T cells in circulation showed marked clonal overlap with drug-bound CD8 T cells from synovial fluid. These results suggest that ICI therapy directly targets CD8 T cells in patients who develop ICI-arthritis and induces an autoimmune pathology that is distinct from prototypical spontaneous autoimmune arthritides.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.add1591","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T13:58:06Z","timestamp":1690552686000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":69,"title":["Clonally expanded CD38\n                    <sup>hi<\/sup>\n                    cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor\u2013associated arthritis"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9536-2845","authenticated-orcid":true,"given":"Runci","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Inflammation, Immunity, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA."},{"name":"Shanghai Institute of Rheumatology\/Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3109-6354","authenticated-orcid":true,"given":"Anvita","family":"Singaraju","sequence":"additional","affiliation":[{"name":"HSS Research Institute, Hospital for Special Surgery, New\u00a0York, NY 10021, USA."},{"name":"Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New\u00a0York, NY 10065, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1524-7159","authenticated-orcid":true,"given":"Kathryne E.","family":"Marks","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, Immunity, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2502-2049","authenticated-orcid":true,"given":"Lorien","family":"Shakib","sequence":"additional","affiliation":[{"name":"HSS Research Institute, Hospital for Special Surgery, New\u00a0York, NY 10021, USA."},{"name":"Graduate Program in Physiology, Biophysics and Systems Biology, Weill Cornell Graduate School of Medical Sciences, New\u00a0York, NY 10065, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2627-0506","authenticated-orcid":true,"given":"Garrett","family":"Dunlap","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, Immunity, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA."},{"name":"Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, 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