A tolerogenic semimature dendritic cells induce effector T-cell hyporesponsiveness by activation of antigen-specific CD4+CD25+T regulatory cells that promotes skin allograft survival in mice
A tolerogenic semimature dendritic cells induce effector T-cell hyporesponsiveness by activation of antigen-specific CD4+CD25+T regulatory cells that promotes skin allograft survival in mice
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DOI：
10.1016/j.cellimm.2009.11.003
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Huang, Jie-fu
中科院分区：
文献类型：
--
作者：
Fu, Bi-mang;He, Xiao-shun;Huang, Jie-fu
半成熟树突状细胞（smDC）可通过激活宿主抗原特异性CD 4（+）CD 25（+）调节性T（Treg）细胞诱导自身免疫耐受。我们假设供体smDC注射到受体体内会通过激活CD 4（+）CD 25（+）Treg细胞诱导效应T细胞低反应性，并促进皮肤移植物存活。骨髓smDC在体外来源于C57 BL/6 J小鼠（供体）。BALB/c小鼠（受体）注射smDC以在体内产生抗原特异性CD 4（+）CD 25（+）Treg细胞。当BALB/c受体在移植前接受C57 BL/6 J smDC或在移植后接受C57 BL/6 J smDC衍生的CD 4（+）CD 25（+）Treg细胞时，同种异体移植物存活时间延长，并且无论雷帕霉素治疗如何，来自这些移植物的皮瓣显示出最高的IL-10产生。我们的研究结果证实，smDC构成DC的独立亚群，其在诱导CD 4（+）CD 25（+）Treg细胞表达高水平IL-10，从而诱导效应T细胞的低反应性方面发挥关键作用。用供体smDC预处理受体可能具有诱导移植耐受的潜力。(C)2009 Elsevier Inc. All rights reserved.
Semimature dendritic cells (smDCs) can induce autoimmune tolerance by activation of host antigen-specific CD4(+)CD25(+) regulatory T (Treg) cells. We hypothesized that donor smDCs injected into recipients would induce effector T-cell hyporesponsiveness by activating CD4(+)CD25(+)Treg cells, and promote skin allograft survival. Myeloid smDCs were derived from C57BL/6J mice (donors) in vitro. BALB/c mice (recipients) were injected with smDCs to generate antigen-specific CD4(+)CD25(+)Treg cells in vivo. Allograft survival was prolonged when BALB/c recipients received either C57BL/6J smDCs prior to grafting or C57BL/6J smDC-derived CD4(+)CD25(+)Treg cells post-grafting, and skin flaps from these grafts showed the highest IL-10 production regardless of rapamycin treatments. Our findings confirm that smDCs constitute an independent subgroup of DCs that play a key role for inducing CD4(+)CD25(+)Treg cells to express high IL-10 levels, which induce hyporesponsiveness of effector T cells. Pre-treating recipients with donor smDCs may have potential for transplant tolerance induction. (C) 2009 Elsevier Inc. All rights reserved.