{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:17:18Z","timestamp":1790471838873,"version":"4.1.0"},"reference-count":198,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T00:00:00Z","timestamp":1550016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI049360 and AI109962"],"award-info":[{"award-number":["AI049360 and AI109962"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Lymphocytic choriomeningitis virus (LCMV) is a paradigm-forming experimental system with a remarkable track record of contributing to the discovery of many of the fundamental concepts of modern immunology. The ability of LCMV to establish a chronic infection in immunocompetent adult mice was instrumental for identifying T cell exhaustion and this system has been invaluable for uncovering the complexity, regulators, and consequences of this state. These findings have been directly relevant for understanding why ineffective T cell responses commonly arise during many chronic infections including HIV and HCV, as well as during tumor outgrowth. The principal feature of exhausted T cells is the inability to elaborate the array of effector functions necessary to contain the underlying infection or tumor. Using LCMV to determine how to prevent and reverse T cell exhaustion has highlighted the potential of checkpoint blockade therapies, most notably PD-1 inhibition strategies, for improving cellular immunity under conditions of antigen persistence. Here, we discuss the discovery, properties, and regulators of exhausted T cells and highlight how LCMV has been at the forefront of advancing our understanding of these ineffective responses.<\/jats:p>","DOI":"10.3390\/v11020156","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T03:21:46Z","timestamp":1550114506000},"page":"156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Immune Exhaustion: Past Lessons and New Insights from Lymphocytic Choriomeningitis Virus"],"prefix":"10.3390","volume":"11","author":[{"given":"Shannon M.","family":"Kahan","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan J.","family":"Zajac","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.2307\/4581290","article-title":"Experimental Lymphocytic Choriomeningitis of Monkeys and Mice Produced by a Virus Encountered in Studies of the 1933 St. Louis Encephalitis Epidemic","volume":"49","author":"Armstrong","year":"1934","journal-title":"Public Health Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1126\/science.81.2099.298","article-title":"A Filterable Virus Recovered from White Mice","volume":"81","author":"Traub","year":"1935","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S0140-6736(05)73191-3","article-title":"The Nobel Chronicles","volume":"356","author":"Raju","year":"2000","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/S0140-6736(05)76313-3","article-title":"The Nobel Chronicles","volume":"353","author":"Raju","year":"1999","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1084\/jem.160.2.521","article-title":"Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. 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