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Our studies demonstrated several deleterious age-related changes in the pool of Ag-specific CD8 T cells that respond to infection. The majority of CD8 T cells from uninfected aged mice was CD44Hi and had increased expression of inhibitory receptors including PD1, LAG3, 2B4, and CD160. These aged CD44Hi CD8 T cells were transcriptionally similar to exhausted CD8 T cells found during chronic infections. In addition, the number of virus-specific precursors in aged mice prior to infection was decreased up to 10-fold, and many of these Ag-specific precursors had high expression of CD44 and PD1. Finally, TCR transgenic studies demonstrated that the CD44Hi Ag-specific CD8 T cells from unimmunized aged and young mice were qualitatively inferior compared with CD44Lo CD8 T cells from aged or young donors. Thus, a decrease in precursor frequency as well as qualitative changes of CD8 T cells during aging are directly related to impaired immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.1101098","type":"journal-article","created":{"date-parts":[[2012,1,14]],"date-time":"2012-01-14T07:47:07Z","timestamp":1326527227000},"page":"1933-1941","source":"Crossref","is-referenced-by-count":123,"title":["Defective CD8 T Cell Responses in Aged Mice Are Due to Quantitative and Qualitative Changes in Virus-Specific Precursors"],"prefix":"10.1093","volume":"188","author":[{"given":"Vilma","family":"Decman","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104"},{"name":"Institute for Immunology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J","family":"Laidlaw","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104"},{"name":"Institute for Immunology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis A","family":"Doering","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104"},{"name":"Institute for Immunology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine , New Haven, CT 06510"},{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hildegund C J","family":"Ertl","sequence":"additional","affiliation":[{"name":"Immunology Program, Wistar Institute , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine , New Haven, CT 06510"},{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E John","family":"Wherry","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104"},{"name":"Institute for Immunology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,2,15]]},"reference":[{"key":"2025032409523614500_r1","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.exger.2006.11.005","article-title":"Telomerase induction in T cells: a cure for aging and disease?","volume":"42","author":"Effros","year":"2007","journal-title":"Exp. 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