{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:28:39Z","timestamp":1792456119884,"version":"4.5.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      The cestode\n                      <jats:italic toggle=\"yes\">Echinococcus multilocularis<\/jats:italic>\n                      infection, a serious health problem worldwide, causes alveolar echinococcosis (AE), a tumor\u2010like disease predominantly located in the liver and able to spread to any organs. Until now, there have been few studies that explore how T\u2010cell exhaustion contributes to the parasite\u2019s escape from immune attack and how it might be reversed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      In this study, we found that liver T\u2010cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine\u2010based inhibitory motif domain (TIGIT) expression was significantly enhanced and positively correlated with lesion activity in AE patients. High TIGIT expression in both liver\u2010infiltrating and blood T cells was associated with their functional exhaustion, and its ligand CD155 was highly expressed by hepatocytes surrounding the infiltrating lymphocytes. In co\u2010culture experiments using human blood T cells and hepatic cell line HL\u20107702, CD155 induced functional impairment of TIGIT\n                      <jats:sup>+<\/jats:sup>\n                      T cells, and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      blockade with TIGIT antibody restored the function of AE patients\u2019 T cells. Similar TIGIT\u2010related functional exhaustion of hepatic T cells and an abundant CD155 expression on hepatocytes were observed in\n                      <jats:italic toggle=\"yes\">E. multilocularis<\/jats:italic>\n                      \u2013infected mice. Importantly,\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      blocking TIGIT prevented T\u2010cell exhaustion and inhibited disease progression in\n                      <jats:italic toggle=\"yes\">E. multilocularis\u2013<\/jats:italic>\n                      infected mice. Mechanistically, CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells were totally and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells partially required for anti\u2010TIGIT\u2013induced regression of parasite growth in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study demonstrates that\n                      <jats:italic toggle=\"yes\">E. multilocularis<\/jats:italic>\n                      can induce T\u2010cell exhaustion through inhibitory receptor TIGIT, and that blocking this checkpoint may reverse the functional impairment of T cells and represent a possible approach to immunotherapy against AE.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.30896","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T03:15:12Z","timestamp":1565752512000},"page":"1297-1315","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":69,"title":["Immune Exhaustion of T Cells in Alveolar Echinococcosis Patients and Its Reversal by Blocking Checkpoint Receptor TIGIT in a Murine Model"],"prefix":"10.1097","volume":"71","author":[{"given":"Chuanshan","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Xinjiang Medical University, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"},{"name":"Basic Medical College,Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyong","family":"Lin","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Echinococcosis, Clinical Medicine Institute, WHO Collaborating Centre on Prevention and Case Management of Echinococcosis,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhide","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Xinjiang Medical University, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central 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University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5633-2317","authenticated-orcid":false,"given":"Abudusalamu","family":"Aini","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Xinjiang Medical University, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Xinjiang Medical University, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical 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Technology,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Chronic Disease Laboratory, Institutes for Life Sciences and School of Medicine,South China University of Technology,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongde","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Echinococcosis, Clinical Medicine Institute, WHO 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