{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:21:03Z","timestamp":1784640063901,"version":"3.55.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"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":[[2014,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The T cell Ig- and mucin domain\u2013containing molecule-3 (Tim-3) negative immune checkpoint receptor demarcates functionally exhausted CD8+ T cells arising from chronic stimulation in viral infections like HIV. Tim-3 blockade leads to improved antiviral CD8+ T cell responses in vitro and, therefore, represents a novel intervention strategy to restore T cell function in vivo and protect from disease progression. However, the Tim-3 pathway in the physiologically relevant rhesus macaque SIV model of AIDS remains uncharacterized. We report that Tim-3+CD8+ T cell frequencies are significantly increased in lymph nodes, but not in peripheral blood, in SIV-infected animals. Tim-3+PD-1+CD8+ T cells are similarly increased during SIV infection and positively correlate with SIV plasma viremia. Tim-3 expression was found primarily on effector memory CD8+ T cells in all tissues examined. Tim-3+CD8+ T cells have lower Ki-67 content and minimal cytokine responses to SIV compared with Tim-3\u2212CD8+ T cells. During acute-phase SIV replication, Tim-3 expression peaked on SIV-specific CD8+ T cells by 2 wk postinfection and then rapidly diminished, irrespective of mutational escape of cognate Ag, suggesting non-TCR\u2013driven mechanisms for Tim-3 expression. Thus, rhesus Tim-3 in SIV infection partially mimics human Tim-3 in HIV infection and may serve as a novel model for targeted studies focused on rejuvenating HIV-specific CD8+ T cell responses.<\/jats:p>","DOI":"10.4049\/jimmunol.1400961","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T05:13:59Z","timestamp":1414473239000},"page":"5576-5583","source":"Crossref","is-referenced-by-count":26,"title":["Expansion of Dysfunctional Tim-3\u2013Expressing Effector Memory CD8+ T Cells during Simian Immunodeficiency Virus Infection in Rhesus Macaques"],"prefix":"10.1093","volume":"193","author":[{"given":"Tsuyoshi","family":"Fujita","sequence":"first","affiliation":[{"name":"Department of Tropical Medicine, Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii , Manoa, HI 96813"},{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine , Sendai 980-8575 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J","family":"Burwitz","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR 97006"},{"name":"Oregon National Primate Research Center, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen M","family":"Chew","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii , Manoa, HI 96813"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S","family":"Reed","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR 97006"},{"name":"Oregon National Primate Research Center, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reesab","family":"Pathak","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR 97006"},{"name":"Oregon National Primate Research Center, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Seger","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR 97006"},{"name":"Oregon National Primate Research Center, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiera L","family":"Clayton","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M","family":"Rini","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario A","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine , Sendai 980-8575 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo J","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center , Covington, LA 70433"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott G","family":"Hansen","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR 97006"},{"name":"Oregon National Primate Research Center, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonah B","family":"Sacha","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR 97006"},{"name":"Oregon National Primate Research Center, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishomwa C","family":"Ndhlovu","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Hawaii Center for AIDS, John A. 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