{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:28:41Z","timestamp":1792456121328,"version":"4.5.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by the infection of <jats:italic>Echinococcus multilocularis<\/jats:italic> (<jats:italic>E. multilocularis<\/jats:italic>) larvae. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) produces inhibitory signals and induces T cell exhaustion, thereby inhibiting the parasiticidal efficacy of the liver immune system. Therefore, the purpose of this study is to explore how T-cell exhaustion contributes to AE and whether blocking CTLA-4 could reverse T cell exhaustion. Here we discovered that the expression of CTLA-4 was increased in the infiltrating margin around the lesion of the liver from AE patients by using western blot and immunohistochemistry assay. Multiple fluorescence immunohistochemistry identified that CTLA-4 and CD4\/CD8 molecules were co-localized. For <jats:italic>in vitro<\/jats:italic> experiments, it was found that the sustained stimulation of <jats:italic>E. multilocularis<\/jats:italic> antigen could induce T cell exhaustion, blocking CTLA-4-reversed T cell exhaustion. For <jats:italic>in vivo<\/jats:italic> experiments, the expression of CTLA-4 was increased in the liver of <jats:italic>E. multilocularis<\/jats:italic>-infected mice, and the CTLA-4 and CD4\/CD8 molecules were co-localized. Flow cytometry analysis demonstrated that the percentages of both CD4<jats:sup>+<\/jats:sup> T cells and CD8<jats:sup>+<\/jats:sup> T cells in the liver and peripheral blood were significantly increased and induced T exhaustion. When the mice were treated with anti-CTLA-4 antibodies, the number and weight of the lesions decreased significantly. Meanwhile, the flow cytometry results suggested that blocking CTLA-4 could effectively reverse T cell exhaustion and reactivate immune function. Our work reveals that blocking CTLA-4 could effectively reverse the T cell exhaustion caused by <jats:italic>E. multilocularis<\/jats:italic> and could be used as a novel target for the treatment of AE.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1358361","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T05:05:12Z","timestamp":1711602312000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The expression of CTLA-4 in hepatic alveolar echinococcosis patients and blocking CTLA-4 to reverse T cell exhaustion in Echinococcus multilocularis-infected mice"],"prefix":"10.3389","volume":"15","author":[{"given":"Yuxuan","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tana","family":"Wuren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binjie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haining","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/bs.apar.2016.11.001","article-title":"Global distribution of alveolar and cystic echinococcosis","volume":"95","author":"Deplazes","year":"2017","journal-title":"Adv Parasitol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(03)14573-4","article-title":"Echinococcosis","volume":"362","author":"McManus","year":"2003","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2022.1072730","article-title":"Food-borne zoonotic echinococcosis: A review with special focus on epidemiology","volume":"9","author":"Alvi","year":"2022","journal-title":"Front Vet. 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