Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE
Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE
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DOI：
10.1038/nm1402
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发表时间：
2006-05-01
期刊：
影响因子：
82.9
通讯作者：
Issazadeh-Navikas, Shohreh
中科院分区：
文献类型：
--
作者：
Liu, Yawei;Teige, Ingrid;Issazadeh-Navikas, Shohreh
神经元作为具有主要免疫调节功能的细胞一直被忽视，因为它们不表达主要组织相容性复合体II类。我们的数据表明，神经元是高度免疫调节的细胞，在调节T细胞反应和中枢神经系统(CNS)炎症中起着至关重要的作用。神经元通过B7-CD28和转化生长因子-β1-转化生长因子-β受体信号通路诱导活化的CD4+T细胞增殖，通过磷酸化的ZAP-70、IL-2和IL-9放大T细胞受体信号。神经元和T细胞之间的相互作用导致脑源性T细胞转化为CD25(+)转化生长因子-β1(+)CTLA-4(+)FoxP3(+)T调节(T-reg)细胞，从而抑制脑源性T细胞和抑制实验性自身免疫性脑脊髓炎。抑制依赖于细胞毒性T淋巴细胞抗原(CTLA)-4，而不是转化生长因子-β1。然而，转化生长因子-β1的自分泌作用对于T-reg细胞的增殖停滞是重要的。阻断B7和转化生长因子-β通路可阻止中枢神经系统特异性Treg细胞的产生。这些发现表明，中枢神经系统中神经元依赖的Treg细胞的产生在调节中枢神经系统炎症中起着重要作用。
Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta 1-TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL- 9. The interaction between neurons and T cells results in the conversion of encephalitogenic T cells to CD25(+) TGF-beta 1(+)CTLA-4(+)FoxP3(+) T regulatory (T-reg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4 but not TGF-beta 1. Autocrine action of TGF-beta 1, however, is important for the proliferative arrest of T-reg cells. Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of Treg cells. These findings show that generation of neuron-dependent Treg cells in the CNS is instrumental in regulating CNS inflammation.