{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T09:14:15Z","timestamp":1793697255192,"version":"4.5.1"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"39","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,9,30]]},"abstract":"<jats:p>Programmed death-1 (PD-1) regulates T cell exhaustion during chronic infections. Blocking the PD-1:PD-ligand (PD-L) pathway reinvigorates exhausted CD8 T cells. Exactly how blocking PD-1:PD-L interactions improves T cell immunity, however, remains unclear. PD-1:PD-L blockade could reprogram all exhausted T cells to become antiviral effectors. Alternatively, this blockade might selectively expand a subset of exhausted T cells. We have identified two subpopulations of exhausted CD8 T cells during chronic viral infection in mice. One subset of exhausted CD8 T cells is rescued by \u03b1PD-L1 blockade, whereas the other subset appears more terminally differentiated and responds poorly to PD-1:PD-L blockade. Blocking PD-1:PD-L interactions reduces spontaneous apoptosis and enhances expansion and protective immunity of the rescuable subset, but not the more terminally differentiated subset of exhausted CD8 T cells. These results have implications for predicting clinical responses to PD-1-based therapeutic interventions and for understanding T cell dynamics during persisting infections.<\/jats:p>","DOI":"10.1073\/pnas.0801497105","type":"journal-article","created":{"date-parts":[[2008,9,22]],"date-time":"2008-09-22T20:45:06Z","timestamp":1222116306000},"page":"15016-15021","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":561,"title":["Selective expansion of a subset of exhausted CD8 T cells by \u03b1PD-L1 blockade"],"prefix":"10.1073","volume":"105","author":[{"given":"Shawn D.","family":"Blackburn","sequence":"first","affiliation":[{"name":"*Immunology Program, The Wistar Institute, Philadelphia, PA 19104; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haina","family":"Shin","sequence":"additional","affiliation":[{"name":"*Immunology Program, The Wistar Institute, Philadelphia, PA 19104; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon J.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Center, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. John","family":"Wherry","sequence":"additional","affiliation":[{"name":"*Immunology Program, The Wistar Institute, Philadelphia, PA 19104; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,9,30]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1443"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04444"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022235"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.05.005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05115"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061496"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1482"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-09-044826"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01177-06"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02021-06"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02844-06"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.7.3532-3540.2006"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0306-227"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.8.4911-4927.2003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.09.006"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1515"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2530"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.14.8960-8968.2005"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071949"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-069112"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00024-07"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.02.033"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni889"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02632-06"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0801497105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:43:59Z","timestamp":1649781839000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0801497105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9,30]]},"references-count":24,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2008,9,30]]}},"alternative-id":["10.1073\/pnas.0801497105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0801497105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9,30]]},"assertion":[{"value":"2008-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-09-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}