{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:07:24Z","timestamp":1760234844545,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"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":["AI085043"],"award-info":[{"award-number":["AI085043"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN148386"],"award-info":[{"award-number":["FDN148386"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>During chronic viral infections, CD8 T cells rapidly lose antiviral and immune-stimulatory functions in a sustained program termed exhaustion. In addition to this loss of function, CD8 T cells with the highest affinity for viral antigen can be physically deleted. Consequently, treatments designed to restore function to exhausted cells and control chronic viral replication are limited from the onset by the decreased breadth of the antiviral T cell response. Yet, it remains unclear why certain populations of CD8 T cells are deleted while others are preserved in an exhausted state. We report that CD8 T cell deletion during chronic viral infection can be prevented by therapeutically lowering viral replication early after infection. The initial resistance to deletion enabled long-term maintenance of antiviral cytolytic activity of the otherwise deleted high-affinity CD8 T cells. In combination with decreased virus titers, CD4 T cell help and prolonged interactions with costimulatory molecules B7-1\/B7-2 were required to prevent CD8 T cell deletion. Thus, therapeutic strategies to decrease early virus replication could enhance virus-specific CD8 T cell diversity and function during chronic infection.<\/jats:p>","DOI":"10.3390\/v13071189","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T22:10:59Z","timestamp":1624399859000},"page":"1189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prevention of CD8 T Cell Deletion during Chronic Viral Infection"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7763-8764","authenticated-orcid":false,"given":"David G.","family":"Brooks","sequence":"first","affiliation":[{"name":"Viral Immunobiology Laboratory, Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA"},{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada"},{"name":"Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoinette","family":"Tishon","sequence":"additional","affiliation":[{"name":"Viral Immunobiology Laboratory, Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B. A.","family":"Oldstone","sequence":"additional","affiliation":[{"name":"Viral Immunobiology Laboratory, Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9568-545X","authenticated-orcid":false,"given":"Dorian B.","family":"McGavern","sequence":"additional","affiliation":[{"name":"Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, 10 Center Drive, Bethesda, MD 20895, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"Barber","year":"2006","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/nm1492","article-title":"Interleukin-10 determines viral clearance or persistence in vivo","volume":"12","author":"Brooks","year":"2006","journal-title":"Nat. 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