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In this study, we show that in primary CMV infections, CD4+CD28\u2212 T cells emerge just after cessation of the viral load, indicating that infection with CMV triggers the formation of CD4+CD28\u2212 T cells. In line with this, we found these cells only in CMV-infected persons. CD4+CD28\u2212 cells had an Ag-primed phenotype and expressed the cytolytic molecules granzyme B and perforin. Importantly, CD4+CD28\u2212 cells were to a large extent CMV-specific because proliferation was only induced by CMV-Ag, but not by recall Ags such as purified protein derivative or tetanus toxoid. CD4+CD28\u2212 cells only produced IFN-\u03b3 after stimulation with CMV-Ag, whereas CD4+CD28+ cells also produced IFN-\u03b3 in response to varicella-zoster virus and purified protein derivative. Thus, CD4+CD28\u2212 T cells emerge as a consequence of CMV infection.<\/jats:p>","DOI":"10.4049\/jimmunol.173.3.1834","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T23:38:25Z","timestamp":1398209905000},"page":"1834-1841","source":"Crossref","is-referenced-by-count":318,"title":["Emergence of a CD4+CD28\u2212 Granzyme B+, Cytomegalovirus-Specific T Cell Subset after Recovery of Primary Cytomegalovirus Infection"],"prefix":"10.1093","volume":"173","author":[{"given":"Ester M M","family":"van Leeuwen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Divisions of Nephrology and Clinical Immunology and Rheumatology , Amsterdam ,","place":["The Netherlands"]},{"name":"Laboratory for Experimental Immunology , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester B M","family":"Remmerswaal","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Immunology , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille T M","family":"Vossen","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Immunology , Amsterdam ,","place":["The Netherlands"]},{"name":"Emma Children\u2019s Hospital , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajda T","family":"Rowshani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Divisions of Nephrology and Clinical Immunology and Rheumatology , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline M E","family":"Wertheim-van Dillen","sequence":"additional","affiliation":[{"name":"Department of Virology, Academic Medical Center , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene\u0301 A W","family":"van Lier","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Immunology , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ineke J M","family":"ten Berge","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Divisions of Nephrology and Clinical Immunology and Rheumatology , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,8,1]]},"reference":[{"key":"2026020212083171900_R1","first-page":"5954","volume-title":"J. 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