{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:23:52Z","timestamp":1790421832522,"version":"4.1.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The chronic presence of viral Ags can induce T cell exhaustion, which is characterized by upregulation of coinhibitory receptors and loss of T cell function. We studied whether a similar phenomenon occurs after liver transplantation (LTx), when there is continuous exposure to alloantigen. Expression of coinhibitory receptors on circulating CD4+ and CD8+ T cells was analyzed longitudinally in 19 patients until 6 mo after LTx and cross-sectionally in 38 patients late (1\u201312 y) after LTx. Expression of the coinhibitory receptors CD160 and CD244 on circulating CD8+ T cells was already higher 6 mo after LTx compared with pre-LTx, and the elevated expression was sustained late after LTx, with CD244 showing the more prominent increase. The strongest upregulation of CD244 on circulating CD8+ T cells was observed in patients who experienced CMV infection after LTx. CMV infection also was associated with reduced CD8+ T cell proliferation and cytotoxic degranulation in response to alloantigen late after LTx. Purified CD244+CD8+ T cells from LTx patients showed lower proliferative responses to alloantigen, as well as to polyclonal stimulation, than did their CD244\u2212 counterparts. In addition, the CD244+CD8+ T cell population contained the majority of CMV peptide\u2013loaded MHC class I tetramer-binding cells. In conclusion, CMV infection after LTx, rather than persistence of alloantigen, induces the accumulation of dysfunctional CD244+CD8+ T cells in the circulation that persist long-term, resulting in reduced frequencies of circulating alloreactive CD8+ T cells. These results suggest that CMV infection restrains CD8+ T cell alloresponses after LTx.<\/jats:p>","DOI":"10.4049\/jimmunol.1500440","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T02:04:37Z","timestamp":1436839477000},"page":"1838-1848","source":"Crossref","is-referenced-by-count":17,"title":["Cytomegalovirus-Induced Expression of CD244 after Liver Transplantation Is Associated with CD8+ T Cell Hyporesponsiveness to Alloantigen"],"prefix":"10.1093","volume":"195","author":[{"given":"Emmy L D","family":"de Mare-Bredemeijer","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center , Rotterdam 3015 CE ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-lei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center , Rotterdam 3015 CE ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanta","family":"Mancham","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center , Rotterdam 3015 CE ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogier","family":"van Gent","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center , Rotterdam 3015 CE ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"van der Heide-Mulder","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center , Rotterdam 3015 CE ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Leiden University Medical Center , Leiden 2300 RC ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam H M","family":"Heemskerk","sequence":"additional","affiliation":[{"name":"Department of Hematology, Leiden University Medical Center , Leiden 2300 RC ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Surgery, Erasmus MC-University Medical Center , Rotterdam 3015 CE ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc J W","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Erasmus MC-University Medical Center , Rotterdam 3015 CE ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herold J","family":"Metselaar","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center , Rotterdam 3015 CE ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap","family":"Kwekkeboom","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center , Rotterdam 3015 CE ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,15]]},"reference":[{"key":"2025030704034390000_r1","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1002\/hep.26426","article-title":"Prospective multicenter clinical trial of immunosuppressive drug withdrawal in stable adult liver transplant recipients","volume":"58","author":"Ben\u00edtez","year":"2013","journal-title":"Hepatology"},{"key":"2025030704034390000_r2","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1111\/j.1600-6143.2006.01396.x","article-title":"An appraisal of tolerance in liver transplantation","volume":"6","author":"Lerut","year":"2006","journal-title":"Am. 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