{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:44:33Z","timestamp":1791301473141,"version":"4.1.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"15","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    T cell exhaustion and loss of memory potential occur during many chronic viral infections and cancer. We investigated when during chronic viral infection virus-specific CD8 T cells lose the potential to form memory. Virus-specific CD8 T cells from established chronic infection were unable to become memory CD8 T cells if removed from infection. However, at earlier stages of chronic infection, these virus-specific CD8 T cells retained the potential to partially or fully revert to a memory differentiation program after transfer to infection-free mice. Conversely, effector CD8 T cells primed during acute infection were not protected from exhaustion if transferred to a chronic infection. We also tested whether memory and exhausted CD8 T cells arose from different subpopulations of effector CD8 T cells and found that only the KLRG1\n                    <jats:sup>lo<\/jats:sup>\n                    memory precursor subset gave rise to exhausted CD8 T cells. Together, these studies demonstrate that CD8 T cell exhaustion is a progressive developmental process. Early during chronic infection, the fate of virus-specific CD8 T cells remains plastic, while later, exhausted CD8 T cells become fixed in their differentiation state. Moreover, exhausted CD8 T cells arise from the memory precursor and not the terminally differentiated subset of effector CD8 T cells. These studies have implications for our understanding of senescence versus exhaustion and for therapeutic interventions during chronic infection.\n                  <\/jats:p>","DOI":"10.1128\/jvi.00889-12","type":"journal-article","created":{"date-parts":[[2012,5,23]],"date-time":"2012-05-23T22:48:01Z","timestamp":1337813281000},"page":"8161-8170","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":281,"title":["Progressive Loss of Memory T Cell Potential and Commitment to Exhaustion during Chronic Viral Infection"],"prefix":"10.1128","volume":"86","author":[{"given":"Jill M.","family":"Angelosanto","sequence":"first","affiliation":[{"name":"Department of Microbiology and Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn D.","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. John","family":"Wherry","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, 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