{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:07:32Z","timestamp":1791328052287,"version":"4.3.1"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2011,4,1]],"date-time":"2011-04-01T00:00:00Z","timestamp":1301616000000},"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":[[2011,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>T cell dysfunction is an important feature of many chronic viral infections. In particular, it was shown that programmed death-1 (PD-1) regulates T cell dysfunction during chronic lymphocytic choriomeningitis virus infection in mice, and PD-1hi cells exhibit an intense exhausted gene signature. These findings were extended to human chronic infections such as HIV, hepatitis C virus, and hepatitis B virus. However, it is not known if PD-1hi cells of healthy humans have the traits of exhausted cells. In this study, we provide a comprehensive description of phenotype, function, and gene expression profiles of PD-1hi versus PD-1lo CD8 T cells in the peripheral blood of healthy human adults as follows: 1) the percentage of naive and memory CD8 T cells varied widely in the peripheral blood cells of healthy humans, and PD-1 was expressed by the memory CD8 T cells; 2) PD-1hi CD8 T cells in healthy humans did not significantly correlate with the PD-1hi exhausted gene signature of HIV-specific human CD8 T cells or chronic lymphocytic choriomeningitis virus-specific CD8 T cells from mice; 3) PD-1 expression did not directly affect the ability of CD8 T cells to secrete cytokines in healthy adults; 4) PD-1 was expressed by the effector memory compared with terminally differentiated effector CD8 T cells; and 5) finally, an interesting inverse relationship between CD45RA and PD-1 expression was observed. In conclusion, our study shows that most PD-1hi CD8 T cells in healthy adult humans are effector memory cells rather than exhausted cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1001783","type":"journal-article","created":{"date-parts":[[2011,3,8]],"date-time":"2011-03-08T07:54:42Z","timestamp":1299570882000},"page":"4200-4212","source":"Crossref","is-referenced-by-count":223,"title":["Phenotype, Function, and Gene Expression Profiles of Programmed Death-1hi CD8 T Cells in Healthy Human Adults"],"prefix":"10.1093","volume":"186","author":[{"given":"Jaikumar","family":"Duraiswamy","sequence":"first","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris C","family":"Ibegbu","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Masopust","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D","family":"Miller","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Araki","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory H","family":"Doho","sequence":"additional","affiliation":[{"name":"Emory Biomarker Service Center, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramila","family":"Tata","sequence":"additional","affiliation":[{"name":"Strand Life Sciences , Bangalore 560024 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Gupta","sequence":"additional","affiliation":[{"name":"Strand Life Sciences , Bangalore 560024 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Zilliox","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helder I","family":"Nakaya","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30322"},{"name":"Department of Pathology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bali","family":"Pulendran","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30322"},{"name":"Department of Pathology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W Nicholas","family":"Haining","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon J","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA 02115"},{"name":"Department of Medicine, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,4,1]]},"reference":[{"key":"2025032411163448500_r1","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1128\/JVI.78.11.5535-5545.2004","article-title":"Memory CD8 T-cell differentiation during viral infection","volume":"78","author":"Wherry","year":"2004","journal-title":"J. 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