{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:23:37Z","timestamp":1790832217356,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novo Nordisk Foundation","award":["NNF19OC0054518"],"award-info":[{"award-number":["NNF19OC0054518"]}]},{"name":"Novo Nordisk Foundation","award":["NNF19OC0055462"],"award-info":[{"award-number":["NNF19OC0055462"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Patients with chronic hepatitis B (CHB) gradually develop T cell exhaustion, and the inhibitory receptor molecule, cytotoxic T-lymphocyte antigen-4 (CTLA-4), may play a role in this phenomenon. This systematic review investigates the role of CTLA-4 in the development of T cell exhaustion in CHB. A systematic literature search was conducted on PubMed and Embase on 31 March 2023 to identify relevant studies. Fifteen studies were included in this review. A majority of the studies investigating CD8+ T cells demonstrated increased expression of CTLA-4 in CHB patients, though one study found this only in HBeAg-positive patients. Three out of four studies investigating the expression of CTLA-4 on CD4+ T cells found upregulation of CTLA-4. Several studies showed constitutive expression of CLTA-4 on CD4+ regulatory T cells. CTLA-4 blockade resulted in heterogeneous responses for all T cell types, as it resulted in increased T cell proliferation and\/or cytokine production in some studies, while other studies found this only when combining blockade of CTLA-4 with other inhibitory receptors. Although mounting evidence supports a role of CTLA-4 in T cell exhaustion, there is still insufficient documentation to describe the expression and exact role of CTLA-4 in T cell exhaustion in CHB.<\/jats:p>","DOI":"10.3390\/v15051141","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T01:37:09Z","timestamp":1683769029000},"page":"1141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The Role of CTLA-4 in T Cell Exhaustion in Chronic Hepatitis B Virus Infection"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9594-706X","authenticated-orcid":false,"given":"\u00c1sa Didriksen","family":"Apol","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"},{"name":"Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark"},{"name":"Copenhagen Hepatitis C Program (CO-HEP), Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anni Assing","family":"Winckelmann","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark"},{"name":"Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark"},{"name":"Copenhagen Hepatitis C Program (CO-HEP), Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasmus B\u00fclow","family":"Duus","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7815-4806","authenticated-orcid":false,"given":"Jens","family":"Bukh","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark"},{"name":"Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark"},{"name":"Copenhagen Hepatitis C Program (CO-HEP), Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Weis","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"ref_1","unstructured":"WHO (2021). 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