{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:46:40Z","timestamp":1791269200115,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"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":[[2012,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human CMV establishes lifelong persistence after primary infection. Chronic CMV infection is associated with intermittent viral reactivation inducing high frequencies of CD4+ T lymphocytes with potent antiviral and helper properties. Primary CMV infection is characterized by an intense viral replication lasting for several months. The impact of this prolonged exposure to high Ag loads on the functionality of CD4+ T cells remains incompletely understood. In pregnant women with primary CMV infection, we observed that CMV-specific CD4+ T lymphocytes had a decreased capacity to proliferate and to produce IL-2. A very large proportion of CMV-specific CD4+ T cells had downregulated the expression of CD28, a costimulatory molecule centrally involved in the production of IL-2. Unexpectedly, both CD28\u2212 and CD28+CD4+ T cells produced low levels of IL-2. This defective production of IL-2 was part of a larger downregulation of cytokine production. Indeed, CMV-specific CD4+ T cells produced lower amounts of IFN-\u03b3 and TNF-\u03b1 and showed lower functional avidity during primary as compared with chronic infection. Increased programmed death-1 expression was observed in CD28+ CMV-specific CD4+ T cells, and programmed death-1 inhibition increased proliferative responses. These results indicate that primary CMV infection is associated with the exhaustion of CMV-specific CD4+ T cells displaying low functional avidity for viral Ags.<\/jats:p>","DOI":"10.4049\/jimmunol.1101165","type":"journal-article","created":{"date-parts":[[2012,8,4]],"date-time":"2012-08-04T05:02:19Z","timestamp":1344056539000},"page":"2665-2672","source":"Crossref","is-referenced-by-count":75,"title":["Functional Exhaustion of CD4+ T Lymphocytes during Primary Cytomegalovirus Infection"],"prefix":"10.1093","volume":"189","author":[{"given":"Pierre","family":"Antoine","sequence":"first","affiliation":[{"name":"Institute for Medical Immunology, Universit\u00e9 Libre de Bruxelles , 6041 Charleroi,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Olislagers","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Universit\u00e9 Libre de Bruxelles , 6041 Charleroi,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Huygens","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Universit\u00e9 Libre de Bruxelles , 6041 Charleroi,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Lecomte","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Universit\u00e9 Libre de Bruxelles , 6041 Charleroi,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Liesnard","sequence":"additional","affiliation":[{"name":"Virology Department, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles , 1070 Brussels,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Donner","sequence":"additional","affiliation":[{"name":"Gynecology Department, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles , 1070 Brussels,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Marchant","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Universit\u00e9 Libre de Bruxelles , 6041 Charleroi,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,9,1]]},"reference":[{"key":"2025032409224403000_r1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S1473-3099(04)01202-2","article-title":"Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments","volume":"4","author":"Gandhi","year":"2004","journal-title":"Lancet Infect. 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