{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T11:21:52Z","timestamp":1778498512455,"version":"3.51.4"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,9,15]]},"abstract":"<jats:p>The control of many persistent viral infections by Ag-specific cytolytic CD8+ T cells requires a concurrent virus-specific CD4+ Th cell response. This reflects in part a requirement of activated effector CD8+ T cells for paracrine IL-2 production as a growth and survival factor. In human CMV and HIV infection, the majority of differentiated virus-specific CD8+ T cells notably lose the ability to produce IL-2 but also lose expression of CD28, a costimulatory molecule. Analysis of the fraction of memory CD8+ T cells that continue to express CD28 revealed these cells retain the ability to produce IL-2. Therefore, we examined if IL-2 production by CD28\u2212 CD8+ T cells could be restored by introduction of a constitutively expressed CD28 gene. Expression of CD28 in CD28\u2212 CD8+ CMV- and HIV-specific CD8+ T cells reconstituted the ability to produce IL-2, which could sustain an autocrine proliferative response after Ag recognition. These results suggest that the loss of CD28 expression during differentiation of memory\/effector CD8+ T cells represents a decisive step in establishing regulation of responding CD8+ T cells, increasing the dependence on CD4+ Th for proliferation after target recognition, and has implications for the treatment of viral disease with adoptively transferred CD8+ T cells.<\/jats:p>","DOI":"10.1084\/jem.20021288","type":"journal-article","created":{"date-parts":[[2003,9,8]],"date-time":"2003-09-08T22:32:13Z","timestamp":1063060333000},"page":"947-955","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":121,"title":["Restoration of CD28 Expression in CD28\u2212 CD8\n                    <b>+<\/b>\n                    Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production"],"prefix":"10.1084","volume":"198","author":[{"given":"Max S.","family":"Topp","sequence":"first","affiliation":[{"name":"1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley R.","family":"Riddell","sequence":"additional","affiliation":[{"name":"1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109"},{"name":"2Department of Medicine, University of Washington, Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiki","family":"Akatsuka","sequence":"additional","affiliation":[{"name":"1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C.","family":"Jensen","sequence":"additional","affiliation":[{"name":"3Division of Pediatrics, City of Hope National Medical Center, Duarte, CA 90195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph N.","family":"Blattman","sequence":"additional","affiliation":[{"name":"1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109"},{"name":"4Department of Immunology, University of Washington, Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip D.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109"},{"name":"2Department of Medicine, University of Washington, Seattle, WA 98195"},{"name":"4Department of Immunology, University of Washington, Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2003,9,8]]},"reference":[{"key":"2023072512084587400_BIB1","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1084\/jem.187.9.1395","volume":"187","year":"1998","journal-title":"J. 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