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Using a range of mouse genetic models, we uncover a critical tolerogenic axis between the autoimmune regulator, AIRE, and the immune checkpoint molecule, PD-1. Their combined loss induced an early-onset lethal autoimmune syndrome driven by autoreactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells that could not be restrained by regulatory T cells. These data shed light on how central and peripheral tolerance mechanisms work together, and highlight thymic function as a potentially key modifier of responses to anti\u2013PD-1 therapies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2120149119","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T14:14:36Z","timestamp":1649427276000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":17,"title":["PD-1 cooperates with AIRE-mediated tolerance to prevent lethal autoimmune disease"],"prefix":"10.1073","volume":"119","author":[{"given":"Antonia N.","family":"Policheni","sequence":"first","affiliation":[{"name":"Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia"},{"name":"Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charis E.","family":"Teh","sequence":"additional","affiliation":[{"name":"Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia"},{"name":"Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6782-1565","authenticated-orcid":false,"given":"Alissa","family":"Robbins","sequence":"additional","affiliation":[{"name":"Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia"},{"name":"Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2406-1479","authenticated-orcid":false,"given":"Selma","family":"Tuzlak","sequence":"additional","affiliation":[{"name":"Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia"},{"name":"Institute for Experimental Immunology, University of Zurich, Zurich CH-8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Strasser","sequence":"additional","affiliation":[{"name":"Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia"},{"name":"Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8457-8242","authenticated-orcid":false,"given":"Daniel H. 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