Inhibition of T-cell responses by hepatic stellate cells via B7-H1-mediated T-cell apoptosis in mice
Inhibition of T-cell responses by hepatic stellate cells via B7-H1-mediated T-cell apoptosis in mice
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DOI：
10.1002/hep.20488
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发表时间：
2004-12-01
期刊：
影响因子：
13.5
通讯作者：
Qian, SG
中科院分区：
文献类型：
--
作者：
Yu, MC;Chen, CH;Qian, SG
在损伤的肝脏中，肝星状细胞分泌多种不同的细胞因子，募集淋巴细胞，从而积极参与肝脏疾病的发病过程。造血干细胞在免疫应答中的作用尚不清楚。在本研究中，从C57BL/10 （H2(b)）小鼠中分离的造血干细胞在静止阶段表达少量关键表面分子。活化的造血干细胞表达主要组织相容性复合体1类共刺激分子，并产生多种细胞因子。干扰素γ (ifn - γ)或活化T细胞的刺激增强了这些分子的表达。有趣的是，激活的（但不是静止的）造血干细胞的添加以剂量依赖的方式抑制了T细胞对胸腺嘧啶的摄取，这些T细胞受到同种抗原或抗cd3介导的T细胞受体连接的刺激。T细胞产生的高细胞因子表明，这种抑制可能不是抑制它们的激活的结果。在USE稀释试验中，t细胞分裂也正常。造血干细胞诱导的t细胞低反应性与t细胞凋亡增强有关。造血干细胞的活化与B7-H1的表达显著增强相关。阻断B7-H1/PD-1连接可显著降低HSC免疫调节活性，提示B7-H1在其中发挥重要作用。综上所述，造血干细胞与免疫细胞之间的双向相互作用可能有助于肝脏免疫耐受。
In the injured liver, hepatic stellate cells (HSCs) secrete many different cytokines, recruit lymphocytes, and thus participate actively in the pathogenesis of liver disease. Little is known of the role of HSCs in immune responses. In this study, HSCs isolated from C57BL/10 (H2(b)) mice were found to express scant key surface molecules in the quiescent stage. Activated HSCs express major histocompatibility complex class 1, costimulatory molecules, and produce a variety of cytokines. Stimulation by interferon gamma (IFN-gamma) or activated T cells enhanced expression of these molecules. Interestingly, addition of the activated (but not quiescent) HSCs suppressed thymidine uptake by T cells that were stimulated by alloantigens or by anti-CD3-mediated T-cell receptor ligation in a dose-dependent manner. High cytokine production by the T cells suggests that the inhibition was probably not a result of suppression of their activation. T-cell division was also found to be normal in a USE dilution assay. The HSC-induced T-cell hyporesponsiveness was associated with enhanced T-cell apoptosis. Activation of HSCs was associated with markedly enhanced expression of B7-H1. Blockade of B7-H1/PD-1 ligation significantly reduced HSC immunomodulatory activity, suggesting an important role of B7-H1. In conclusion, the bidirectional interactions between HSCs and immune cells may contribute to hepatic immune tolerance.