Liver-primed CD8+ T cells suppress antiviral adaptive immunity through galectin-9-independent T-cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice.
Liver-primed CD8+ T cells suppress antiviral adaptive immunity through galectin-9-independent T-cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice.
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DOI：
10.1002/hep.26938
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发表时间：
2014-04
期刊：
影响因子：
13.5
通讯作者：
Hahn, Young S.
中科院分区：
文献类型：
--
作者：
Dolina, Joseph S.;Braciale, Thomas J.;Hahn, Young S.
肝脏是持续性感染（如乙型肝炎B（HBV）和丙型肝炎（HCV）病毒）利用的致耐受性环境。在静脉内嗜肝腺病毒感染的鼠模型中，肝脏致敏的抗病毒CD 8 + T细胞不能产生促炎细胞因子，并且不显示由肝外（即皮下）部位感染产生的效应CD 8 + T细胞的细胞溶解活性特征。重要的是，肝脏产生的CD 8 + T细胞似乎还具有T调节（Treg）细胞功能，其通过由CD 8 + Treg细胞表达的T细胞免疫球蛋白和粘蛋白3（Tim-3）在体外和体内限制抗原特异性T效应（Teff）细胞增殖的能力来例证。调节活性不需要识别典型的Tim-3配体，半乳糖凝集素-9，但依赖于CD 8 + Treg细胞表面Tim-3与alarmin，高迁移率族蛋白1（HMGB-1）的结合。结论：在肝脏的急性和慢性病毒感染的情况下，通过HMGB-1识别起作用的病毒特异性Tim-3+ CD 8 + T细胞可能会抑制肝脏微环境中的肝脏T细胞应答，从而限制免疫介导的组织损伤或促进持续感染的建立。（肝病学2014;59：1351-1365）
The liver is a tolerogenic environment exploited by persistent infections, such as hepatitis B (HBV) and C (HCV) viruses. In a murine model of intravenous hepatotropic adenovirus infection, liver-primed antiviral CD8+ T cells fail to produce proinflammatory cytokines and do not display cytolytic activity characteristic of effector CD8+ T cells generated by infection at an extrahepatic, that is, subcutaneous, site. Importantly, liver-generated CD8+ T cells also appear to have a T-regulatory (Treg) cell function exemplified by their ability to limit proliferation of antigen-specific T-effector (Teff) cells in vitro and in vivo via T-cell immunoglobulin and mucin 3 (Tim-3) expressed by the CD8+ Treg cells. Regulatory activity did not require recognition of the canonical Tim-3 ligand, galectin-9, but was dependent on CD8+ Treg cell-surface Tim-3 binding to the alarmin, high-mobility group box 1 (HMGB-1). Conclusion: Virus-specific Tim-3+CD8+ T cells operating through HMGB-1 recognition in the setting of acute and chronic viral infections of the liver may act to dampen hepatic T-cell responses in the liver microenvironment and, as a consequence, limit immune-mediated tissue injury or promote the establishment of persistent infections. (Hepatology 2014;59:1351-1365)
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HMGB1：内源性危险信号。
影响因子：
5.7
作者：
Klune, John R.;Dhupar, Rajeev;Cardinal, Jon;Billiar, Timothy R.;Tsung, Allan
通讯作者：
Tsung, Allan
DOI：
10.4049/jimmunol.182.3.1469
发表时间：
2009-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Strauss L;Bergmann C;Whiteside TL
通讯作者：
Whiteside TL
影响因子：
30.5
作者：
Chiba, Shigeki;Baghdadi, Muhammad;Akiba, Hisaya;Yoshiyama, Hironori;Kinoshita, Ichiro;Dosaka-Akita, Hirotoshi;Fujioka, Yoichiro;Ohba, Yusuke;Gorman, Jacob V.;Colgan, John D.;Hirashima, Mitsuomi;Uede, Toshimitsu;Takaoka, Akinori;Yagita, Hideo;Jinushi, Masahisa
通讯作者：
Jinushi, Masahisa
影响因子：
82.9
作者：
Rangachari, Manu;Zhu, Chen;Sakuishi, Kaori;Xiao, Sheng;Karman, Jozsef;Chen, Andrew;Angin, Mathieu;Wakeham, Andrew;Greenfield, Edward A.;Sobel, Raymond A.;Okada, Hitoshi;McKinnon, Peter J.;Mak, Tak W.;Addo, Marylyn M.;Anderson, Ana C.;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
15.9
作者：
Blackburn, Shawn D.;Wherry, E. John
通讯作者：
Wherry, E. John