B7-H4 Mediates Inhibition of T Cell Responses by Activated Murine Hepatic Stellate Cells

被引：53

作者：

Chinnadurai, Raghavan ^{[1
]}

Grakoui, Arash ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Med Microbiol & Immunol, Emory Vaccine Ctr, Atlanta, GA 30329 USA

来源：

HEPATOLOGY | 2010年 / 52卷 / 06期

关键词：

ANTIGEN-PRESENTING CELLS; B7; FAMILY-MEMBER; HCV INFECTION; LIVER-DISEASE; EXPRESSION; APOPTOSIS; PROLIFERATION; MOLECULES; IMMUNITY; FIBROSIS;

D O I：

10.1002/hep.23953

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Liver fibrosis is mediated by the transformation of hepatic stellate cells (HSC) from a quiescent to an activated state To understand the role of HSC in liver immunity, we investigated the effect of this transition on T cell stimulation in vitro Unlike quiescent HSC, activated HSC did not induce proliferation of antigen-specific T cells Phenotypic analysis of quiescent and activated HSC revealed that activated HSC expressed the coinhibitory molecule B7-H4 Silencing B7-H4 by small interfering RNA (siRNA) in activated HSC restored the ability of T cells to proliferate, differentiate, and regain effector recall responses Furthermore, expression of B7-H4 on HSC inhibits early T cell activation and addition of exogenous interleukin (IL)-2 reversed the T cell anergy induced by activated HSC Conclusion These studies reveal a novel role for activated HSC in the attenuation of intrahepatic T cell responses by way of expression of the coinhibitory molecule B7-H4, and may provide fundamental insight into intrahepatic immunity during liver fibrogenesis (HEPATOLOGY 2010,52 2177-2185)

引用

页码：2177 / 2185

页数：9

共 44 条

[1]

Antigen-specific primary activation of CD8+ T cells within the liver [J].

Bertolino, P ;

Bowen, DG ;

McCaughan, GW ;

Fazekas de St Groth, B .

JOURNAL OF IMMUNOLOGY, 2001, 166 (09) :5430-5438

[2]

Carter LL, 2002, EUR J IMMUNOL, V32, P634, DOI 10.1002/1521-4141(200203)32:3<634::AID-IMMU634>3.0.CO

[3]

2-9

[4]

In vivo immune modulatory activity of hepatic stellate cells in mice [J].

Chen, Cheng-Hsu ;

Kuo, Liang-Mou ;

Chang, Yigang ;

Wu, Wenhan ;

Goldbach, Christina ;

Ross, Mark A. ;

Stolz, Donna B. ;

Chen, Liepin ;

Fung, John J. ;

Lu, Lin ;

Qian, Shiguang .

HEPATOLOGY, 2006, 44 (05) :1171-1181

[5]

Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity [J].

Chen, LP .

NATURE REVIEWS IMMUNOLOGY, 2004, 4 (05) :336-347

[6]

Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family [J].

Choi, IH ;

Zhu, GF ;

Sica, GL ;

Strome, SE ;

Cheville, JC ;

Lau, JS ;

Zhu, YW ;

Flies, DB ;

Tamada, K ;

Chen, LP .

JOURNAL OF IMMUNOLOGY, 2003, 171 (09) :4650-4654

[7]

The liver as a site of T-cell apoptosis: graveyard, or krilling field? [J].

Crispe, IN ;

Dao, T ;

Klugewitz, K ;

Mehal, WZ ;

Metz, DP .

IMMUNOLOGICAL REVIEWS, 2000, 174 :47-62

[8]

B7-H1 determines accumulation and deletion of intrahepatic CD8+ T lymphocytes [J].

Dong, HD ;

Zhu, GF ;

Tamada, K ;

Flies, DB ;

van Deursen, JMA ;

Chen, LP .

IMMUNITY, 2004, 20 (03) :327-336

[9]

IL-2 signaling prevents T cell anergy by inhibiting the expression of anergy-inducing genes [J].

Dure, Myrianne ;

Macian, Fernando .

MOLECULAR IMMUNOLOGY, 2009, 46 (05) :999-1006

[10]

Mechanisms of hepatic fibrogenesis [J].

Friedman, Scott L. .

GASTROENTEROLOGY, 2008, 134 (06) :1655-1669

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