Human Placental Pericytes Poorly Stimulate and Actively Regulate Allogeneic CD4 T Cell Responses
Human Placental Pericytes Poorly Stimulate and Actively Regulate Allogeneic CD4 T Cell Responses
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DOI：
10.1161/atvbaha.110.217117
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发表时间：
2011-01-01
影响因子：
8.7
通讯作者：
Pober, Jordan S.
中科院分区：
文献类型：
--
作者：
Maier, Cheryl L.;Pober, Jordan S.
目的：外周组织细胞介导的免疫反应始于T细胞通过内皮细胞(EC)微血管的渗入和周细胞(PC)占据的血管周围空间积聚。在这里，我们研究人类T细胞如何与PC相互作用。方法和结果--我们比较了人胎盘PC和自体脐静脉EC。与EC相比，培养的PC表达较低水平的主要组织相容性复合体(MHC)和阳性共刺激分子，而表达较高水平的负共刺激分子。与EC不同，经干扰素治疗的MHC II类阳性PC(PC+)不能刺激静息的同种异体CD4T细胞的增殖或细胞因子的产生。相反，静息的CD4T细胞与PC+共培养会诱导CD25的表达，并使T细胞对同一捐赠者的EC+的重新刺激没有反应。结论人胎盘PC免疫原性较差，可通过接触依赖和非接触机制负性调节CD4T细胞对EC+的反应。(动脉血栓血管生物)2011；31：183-189。)
Objective-Cell-mediated immune responses in peripheral tissues begin with T cell infiltration through endothelial cell (EC) microvessels and accumulation in the perivascular space occupied by pericytes (PC). Here, we investigate how human T cells interact with PC.Methods and Results-We compared human placental PC with autologous umbilical vein EC. Cultured PC express lower levels of major histocompatibility complex (MHC) and positive costimulatory molecules but higher levels of negative costimulatory molecules than do EC. Unlike EC, interferon-gamma-treated MHC class II-positive PC (PC+) cannot stimulate resting allogeneic CD4 T cell proliferation or cytokine production. Instead, coculture of resting CD4 T cells with PC+ induces CD25 expression and renders T cells unresponsive to restimulation by EC+ from the same donor. PC cultured across a semi-permeable membrane decrease alloreactive CD4 T cell proliferation to EC+, an effect enhanced by pretreatment of PC with interferon-gamma and partially reversed by interleukin-10 and transforming growth factor-beta neutralization, but do not induce anergy.Conclusion-Human placental PC are poorly immunogenic and negatively regulate CD4 T cell responses through contact-dependent and contact-independent mechanisms. (Arterioscler Thromb Vasc Biol. 2011;31:183-189.)