{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:32:30Z","timestamp":1789565550210,"version":"build-2803163510"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"102","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2024,12,20]]},"abstract":"<jats:p>\n                    The increasing use of anti\u2013programmed cell death 1 (PD-1) immune checkpoint blockade has led to the emergence of immune-related adverse events (irAEs), including dysfunction of the submandibular gland (SMG). In this study, we investigated the immunoregulatory mechanism contributing to the susceptibility of the SMG to irAEs. We found that the SMGs of PD-1\u2013deficient mice and anti\u2013programmed cell death ligand 1 (PD-L1)\u2013treated mice harbor an expanded population of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. We demonstrate that natural killer (NK) cells expressing PD-L1 tightly regulate CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the SMG. When this immunoregulation is disrupted, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells clonally expand and acquire a unique transcriptional profile consistent with T cell receptor (TCR) activation. These clonally expanded cells phenotypically overlapped with cytotoxic GzmK\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T autoimmune cells identified in patients with primary Sj\u00f6gren\u2019s syndrome. Understanding how NK cells modulate CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activity in the SMG opens new avenues for preventing irAEs in patients undergoing checkpoint blockade therapies.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.adl2967","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T13:58:34Z","timestamp":1734703114000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":16,"title":["NK cells restrain cytotoxic CD8\n                    <sup>+<\/sup>\n                    T cells in the submandibular gland via PD-1\u2013PD-L1"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4960-131X","authenticated-orcid":true,"given":"Samantha M.","family":"Borys","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9465-706X","authenticated-orcid":true,"given":"Shanelle P.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1280-3365","authenticated-orcid":true,"given":"Ian","family":"Magill","sequence":"additional","affiliation":[{"name":"Department of Immunology, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-217X","authenticated-orcid":true,"given":"David","family":"Zemmour","sequence":"additional","affiliation":[{"name":"Committee on Immunology, University of Chicago, Chicago, IL 60637, USA."},{"name":"Department of Pathology, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7497-8488","authenticated-orcid":true,"given":"Laurent","family":"Brossay","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01886-x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303469"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601099"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.11.007"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.03.007"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.09.082"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.09.076"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00256-06"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-008-0077-2"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.3.1703-1717.2003"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001254"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.704862"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0823"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.108"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80089-8"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/1758835920937612"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703481"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412082"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2020.04.018"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5502.319"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06217-y"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022125"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep39105"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2016.08.007"},{"key":"e_1_3_2_26_2","first-page":"114","article-title":"Sicca\/Sj\u00f6gren\u2019s syndrome triggered by PD-1\/PD-L1 checkpoint inhibitors. 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