{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:09:24Z","timestamp":1790521764714,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":311,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["AVPRS0015"],"award-info":[{"award-number":["AVPRS0015"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R37CA263592"],"award-info":[{"award-number":["R37CA263592"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31CA261058"],"award-info":[{"award-number":["F31CA261058"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"OHSU Foundation","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inhibitory proteins, such as programmed cell death protein 1 (PD-1), have been studied extensively in peripheral T cell responses to foreign Ags, self-Ags, and neoantigens. Notably, these proteins are first expressed during T cell development in the thymus. Reports suggest that PD-1 limits regulatory T cell (Treg) development, but the mechanism by which PD-1 exerts this function remains unknown. The present study expands the evaluation of murine PD-1 and its ligands in the thymus, demonstrating that some of the highest expressers of PD-1 and programmed death-ligand 1 are agonist selected cells. Surprisingly, we reveal a selective role for PD-1 in regulating the developmental niche only for Tregs because other agonist selected cell populations, such as NK T cells, remain unchanged. We also ruled out PD-1 as a regulator of proliferation or cell death of agonist selected Tregs and further demonstrated that PD-1\u2013deficient Tregs have reduced TCR signaling. Unexpectedly, the data suggest that PD-1\u2013deficient thymocytes produce elevated levels of IL-2, a Treg niche\u2013limiting cytokine. Collectively, these data suggest a novel role for PD-1 in regulating IL-2 production and the concurrent agonist selection of murine thymic Tregs. This observation has implications for the use of checkpoint blockade in the context of cancer and infection.<\/jats:p>","DOI":"10.4049\/immunohorizons.2300079","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T12:37:07Z","timestamp":1711715827000},"page":"281-294","source":"Crossref","is-referenced-by-count":2,"title":["PD-1 Limits IL-2 Production and Thymic Regulatory T Cell Development"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1519-8131","authenticated-orcid":false,"given":"Breanna","family":"Caruso","sequence":"first","affiliation":[{"name":"Cell, Developmental and Cancer Biology, Oregon Health and Science University , Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin R","family":"Weeder","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Oregon Health and Science University , Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reid F","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Oregon Health and Science University , Portland, OR"},{"name":"Knight Cancer Institute, Oregon Health and Science University , Portland, OR"},{"name":"Department of Radiation Medicine, Oregon Health and Science University , Portland, OR"},{"name":"Veterans Affairs Portland Health Care System , Portland,OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1952-7737","authenticated-orcid":false,"given":"Amy E","family":"Moran","sequence":"additional","affiliation":[{"name":"Cell, Developmental and Cancer Biology, Oregon Health and Science University , Portland, OR"},{"name":"Knight Cancer Institute, Oregon Health and Science University , Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"2025010608550743100_r1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1146\/annurev.immunol.21.120601.141107","article-title":"Positive and negative selection of T cells","volume":"21","author":"Starr","year":"2003","journal-title":"Annu. 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