{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T15:58:27Z","timestamp":1793289507705,"version":"4.5.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1735,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Multiple inhibitory receptors may play a role in the weak or absent CD81 T-cell response in chronic hepatitis B virus (HBV) infection. Yet few receptors have been characterized in detail and little is known about their complex regulation. In the present study, we investi-gated the role of the signaling lymphocyte activation molecule (SLAM)-related receptor CD244 and of programmed death 1 (PD-1) in HBV infection in 15 acutely and 66 chroni-cally infected patients as well as 9 resolvers and 21 healthy controls. The expression of CD244, PD-1, and T-cell immunoglobulin domain and mucin domain 3 (TIM-3) was an-alyzed in virus-speci\ufb01c CD81 T-cells derived from peripheral blood or liver using major histocompatibility complex class I pentamers targeting immunodominant epitopes of HBV, Epstein-Barr-virus (EBV), or in\ufb02uenza virus (Flu). In chronic HBV infection, virus-speci\ufb01c CD81 T-cells expressed higher levels of CD244 both in the peripheral blood and liver in comparison to the acute phase of infection or following resolution. CD244 was expressed at similarly high levels in EBV infection, but was low on Flu-speci\ufb01c CD81 T-cells. In chronic HBV infection, high-level CD244 expression coincided with an increased expression of PD-1. The inhibition of the CD244 signaling pathway by antibodies directed against either CD244 or its ligand CD48 resulted in an increased virus-speci\ufb01c proliferation and cytotoxicity as measured by the expression of CD107a, interferon-\n                      <jats:italic toggle=\"yes\">c<\/jats:italic>\n                      , and tumor necrosis factor-\n                      <jats:italic toggle=\"yes\">a<\/jats:italic>\n                      in CD81 T-cells.\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                      CD244 and PD-1 are highly coex-pressed on virus-speci\ufb01c CD81 T-cells in chronic HBV infection and blocking CD244 or its ligand CD48 may restore T-cell function independent of the PD-1 pathway. CD244 may thus be another potential target for immunotherapy in chronic viral infec-tions. (HEPATOLOGY 2010;52:1934-1947)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.23936","type":"journal-article","created":{"date-parts":[[2010,8,29]],"date-time":"2010-08-29T19:12:49Z","timestamp":1283109169000},"page":"1934-1947","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":203,"title":["The Immunoregulatory Role of CD244 in Chronic Hepatitis B Infection and its Inhibitory Potential on Virus-Specific CD8+ T-cell 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