{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:39:40Z","timestamp":1791286780688,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T00:00:00Z","timestamp":1283299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>During many chronic infections, the responding CD8 T cells become exhausted as they progressively lose their ability to elaborate key effector functions. Unlike prototypic memory CD8 cells, which rapidly synthesize IFN-\u03b3 following activation, severely exhausted T cells fail to produce this effector molecule. Nevertheless, the ontogeny of exhausted CD8 T cells, as well as the underlying mechanisms that account for their functional inactivation, remains ill defined. We have used cytokine reporter mice, which mark the transcription of IFN-\u03b3 mRNA by the expression of Thy1.1, to decipher how activation events during the early stages of a chronic infection dictate the development of exhaustion. We show that virus-specific CD8 T cells clearly respond during the early stages of chronic lymphocytic choriomeningitis virus infection, and that this early T cell response is more pronounced than that initially observed in acutely infected hosts. Thus, exhausted CD8 T cells appear to emerge from populations of potently activated precursors. Unlike acute infections, which result in massive expansion of the responding T cells, there is a rapid attenuation of further expansion during chronic infections. The exhausted T cells that subsequently emerge in chronically infected hosts are incapable of producing the IFN-\u03b3 protein. Surprisingly, high levels of the IFN-\u03b3 transcript are still present in exhausted cells, demonstrating that ablation of IFN-\u03b3 production by exhausted cells is not due to transcriptional silencing. Thus, posttranscription regulatory mechanisms likely disable this effector module.<\/jats:p>","DOI":"10.4049\/jimmunol.1000841","type":"journal-article","created":{"date-parts":[[2010,8,19]],"date-time":"2010-08-19T02:46:01Z","timestamp":1282185961000},"page":"3643-3651","source":"Crossref","is-referenced-by-count":46,"title":["Pronounced Virus-Dependent Activation Drives Exhaustion but Sustains IFN-\u03b3 Transcript Levels"],"prefix":"10.1093","volume":"185","author":[{"given":"Kathryn J","family":"Mackerness","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen A","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M","family":"Lilly","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey T","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie E","family":"Harrington","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,9,15]]},"reference":[{"key":"2025032411532861500_r1","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/362758a0","article-title":"Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells","volume":"362","author":"Moskophidis","year":"1993","journal-title":"Nature"},{"key":"2025032411532861500_r2","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1084\/jem.188.12.2205","article-title":"Viral immune evasion due to persistence of activated T cells without effector function","volume":"188","author":"Zajac","year":"1998","journal-title":"J. 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