Microglial Activation Milieu Controls Regulatory T Cell Responses
Microglial Activation Milieu Controls Regulatory T Cell Responses
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DOI：
10.4049/jimmunol.1203331
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发表时间：
2013-12-01
影响因子：
4.4
通讯作者：
Nitsch, Robert
中科院分区：
文献类型：
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作者：
Ebner, Friederike;Brandt, Christine;Nitsch, Robert
虽然导致脑特异性炎症和T细胞激活的机制已经被广泛研究，但对大脑中局部固有免疫细胞的调节机制知之甚少。在这项研究中，我们首次发现MHC II类(+)CD40(DIM)CD86(DIM)IL-10(+)小胶质细胞在体外可以有效地诱导抗原特异性的CD4(+)Foxp3(+)调节性T细胞(Treg)。小胶质细胞对MHC-II类分子、共刺激分子和IL-10的表达有不同的调节作用，依赖于干扰素-γ的攻击量和抗原剂量，促进效应T细胞或Treg的诱导。小胶质细胞诱导的Tregs在体外通过抑制效应T细胞的Ag特异性增殖而发挥作用，在体内通过过继移植后减轻实验性自身免疫性脑脊髓炎的病程而发挥作用。这些结果表明，MHC II类(+)、CD40(DIM)、CD86(DIM)、IL-10(+)小胶质细胞可能具有影响中枢神经系统局部免疫反应的调节特性。
Although mechanisms leading to brain-specific inflammation and T cell activation have been widely investigated, regulatory mechanisms of local innate immune cells in the brain are only poorly understood. In this study, to our knowledge we show for the first timethat MHC class II(+)CD40(dim)CD86(dim)IL-10(+) microglia are potent inducers of Ag-specific CD4(+)Foxp3(+) regulatory T cells (Tregs) in vitro. Microglia differentially regulated MHC class II expression, costimulatory molecules, and IL-10 depending on the amount of IFN-gamma challenge and Ag dose, promoting either effector T cell or Treg induction. Microglia-induced Tregs were functionally active in vitro by inhibiting Ag-specific proliferation of effector T cells, and in vivo by attenuating experimental autoimmune encephalomyelitis disease course after adoptive transfer. These results indicate that MHC class II(+)CD40(dim)CD86(dim)IL-10(+) microglia have regulatory properties potentially influencing local immune responses in the CNS.