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The expression of CTLA-4 in hepatic alveolar echinococcosis patients and blocking CTLA-4 to reverse T cell exhaustion in Echinococcus multilocularis-infected mice

dc.contributor.authorYuxuan Yang
dc.contributor.authorYuxuan Yang
dc.contributor.authorTana Wuren
dc.contributor.authorBinjie Wu
dc.contributor.authorBinjie Wu
dc.contributor.authorShilei Cheng
dc.contributor.authorShilei Cheng
dc.contributor.authorHaining Fan
dc.contributor.authorHaining Fan
dc.contributor.otherResearch Center for High Altitude Medicine, Qinghai University, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Laboratory for High Altitude Medicine of Qinghai Province, Xining, Qinghai, China
dc.contributor.otherQinghai Research Key Laboratory for Echinococcosis, Qinghai University, Xining, Qinghai, China
dc.contributor.otherResearch Center for High Altitude Medicine, Qinghai University, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Laboratory for High Altitude Medicine of Qinghai Province, Xining, Qinghai, China
dc.contributor.otherResearch Center for High Altitude Medicine, Qinghai University, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Laboratory for High Altitude Medicine of Qinghai Province, Xining, Qinghai, China
dc.contributor.otherQinghai Research Key Laboratory for Echinococcosis, Qinghai University, Xining, Qinghai, China
dc.contributor.otherResearch Center for High Altitude Medicine, Qinghai University, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Laboratory for High Altitude Medicine of Qinghai Province, Xining, Qinghai, China
dc.contributor.otherQinghai Research Key Laboratory for Echinococcosis, Qinghai University, Xining, Qinghai, China
dc.contributor.otherQinghai Research Key Laboratory for Echinococcosis, Qinghai University, Xining, Qinghai, China
dc.contributor.otherDepartment of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, Qinghai, China
dc.date.accessioned2025-10-09T05:31:54Z
dc.date.available2025-10-09T05:31:54Z
dc.date.issued01-03-2024
dc.identifier.urihttps://www.frontiersin.org/articles/10.3389/fimmu.2024.1358361/full
dc.identifier.urihttp://digilib.fisipol.ugm.ac.id/repo/handle/15717717/41132
dc.description.abstractAlveolar echinococcosis (AE) is a zoonotic parasitic disease caused by the infection of Echinococcus multilocularis (E. multilocularis) 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 in vitro experiments, it was found that the sustained stimulation of E. multilocularis antigen could induce T cell exhaustion, blocking CTLA-4-reversed T cell exhaustion. For in vivo experiments, the expression of CTLA-4 was increased in the liver of E. multilocularis-infected mice, and the CTLA-4 and CD4/CD8 molecules were co-localized. Flow cytometry analysis demonstrated that the percentages of both CD4+ T cells and CD8+ 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 E. multilocularis and could be used as a novel target for the treatment of AE.
dc.language.isoEN
dc.publisherFrontiers Media S.A.
dc.subject.lccImmunologic diseases. Allergy
dc.titleThe expression of CTLA-4 in hepatic alveolar echinococcosis patients and blocking CTLA-4 to reverse T cell exhaustion in Echinococcus multilocularis-infected mice
dc.typeArticle
dc.description.keywordsalveolar echinococcosis
dc.description.keywordsEchinococcus multilocularis
dc.description.keywordsimmune microenvironment
dc.description.keywordscytotoxic T-lymphocyte antigen 4
dc.description.keywordsT cell exhaustion
dc.description.doi10.3389/fimmu.2024.1358361
dc.title.journalFrontiers in Immunology
dc.identifier.e-issn1664-3224
dc.identifier.oaioai:doaj.org/journal:82346988063a4cee85f46a1fe9a41cc9


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