Hepatic stellate cells preferentially expand allogeneic CD4+ CD25+ FoxP3+ regulatory T cells in an IL-2-dependent manner.
Hepatic stellate cells preferentially expand allogeneic CD4+ CD25+ FoxP3+ regulatory T cells in an IL-2-dependent manner.
复制标题
DOI：
10.1097/tp.0b013e31818bfd13
复制
发表时间：
2008-12-15
期刊：
影响因子：
6.2
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
Jiang G;Yang HR;Wang L;Wildey GM;Fung J;Qian S;Lu L
器官移植已经成功地实践了几十年，但细胞移植的结果仍然令人失望。这是动物模型中的情况;小鼠中的肝同种异体移植物是自发接受的，不需要免疫抑制，而相同组合中的肝细胞移植物是急性排斥的，显然是由于免疫攻击，因为同基因肝细胞移植物无限期存活。这表明肝非实质细胞在保护实质细胞免受排斥反应中起重要作用。我们已经证明，肝星状细胞（HpSC），众所周知，参与肝修复和纤维化，介导强有力的免疫调节功能，通过诱导活化的T细胞死亡。本文报道了HpSC经IFN-γ激活后获得抗原提呈能力。与主要刺激CD 4 + T细胞产生CD 25 + Foxp 3 −效应细胞的专职APC树突状细胞（DC）相反，HpSC以IL-2依赖性方式选择性扩增CD 4 + CD 25 + Foxp 3+细胞。这些扩增的CD 4 + CD 25 + Foxp 3+细胞显示调节性T（Treg）细胞活性，以MHC非特异性方式有效抑制T细胞增殖以响应抗CD 3 mAb或同种异体抗原。Treg细胞在IL-2的帮助下从CD 4 + CD 25+群体扩增，不依赖于B7-H1和TGF-β。将HpSC施用到同种异体受体中导致体内CD 4 + CD 25 + FoxP 3+细胞扩增。肝间质HpSC作为非专职APC，优先扩增CD 25 + FoxP 3 + Treg细胞，这可能有助于肝脏的免疫调节。
Organ transplantation has been successfully practice for decades, but the outcome of cell transplantation remains disappointing. This is the case in animal models; liver allografts in mice are spontaneous accepted without requirement of immunosuppression, whereas hepatocyte transplants in the same combination are acutely rejected, apparently resulting from immune attacks because syngeneic hepatocyte transplants survive indefinitely. This suggests that liver non-parenchymal cells play an important role in protecting parenchymal cell from rejection. We have shown that hepatic stellate cells (HpSC), well known to participate in liver repairing and fibrosis, mediate potent immunomodulatory functions via induction of activated T cell death. Here we report that HpSC acquired antigen presenting capacity following activated by IFN-γ. In contrast to professional APC dendritic cells (DC) that predominantly stimulated CD4+ T cells to generate CD25+Foxp3− effector cells, HpSC selectively expanded CD4+CD25+Foxp3+ cells in an IL-2 dependent manner. These expanded CD4+CD25+Foxp3+ cells showed regulatory T (Treg) cell activity in effectively inhibiting T cell proliferation in responses to anti-CD3 mAb or alloantigens in a MHC non-specific fashion. The Treg cells were expanded from the CD4+CD25+ population with the help of IL-2, independent of B7-H1 and TGF-β. Administration of HpSC into allogeneic recipients resulted in expansion of CD4+CD25+FoxP3+ cells in vivo. Liver stromal HpSC acted as non-professional APC, and preferentially expanded CD25+FoxP3+ Treg cells, which may contribute to immune regulation in the liver.