The activation status of neuroantigen-specific T cells in the target organ determines the clinical outcome of autoimmune encephalomyelitis.
The activation status of neuroantigen-specific T cells in the target organ determines the clinical outcome of autoimmune encephalomyelitis.
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DOI：
10.1084/jem.20031064
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发表时间：
2004-01-19
期刊：
影响因子：
--
通讯作者：
Flügel A
中科院分区：
文献类型：
--
作者：
Kawakami N;Lassmann S;Li Z;Odoardi F;Ritter T;Ziemssen T;Klinkert WE;Ellwart JW;Bradl M;Krivacic K;Lassmann H;Ransohoff RM;Volk HD;Wekerle H;Linington C;Flügel A
实验性自身免疫性脑脊髓炎（EAE）的临床表现严重依赖于靶自身抗原的性质和实验动物的遗传背景。在刘易斯大鼠中，髓鞘碱性蛋白（MBP）特异性T细胞介导了潜在致死性EAE，而转移S100β或髓鞘少突胶质细胞糖蛋白（MOG）特异性T细胞可在中枢神经系统（CNS）中引起强烈的炎症反应，且疾病轻微。然而，在黑Agglutinin大鼠中，MOG特异性T细胞的致病性类似于刘易斯大鼠中MBP特异性T细胞的致病性。使用逆转录病毒转导的绿色荧光T细胞，我们现在报告，不同的疾病活动反映了不同水平的自身反应性效应T细胞在其靶组织中的激活。无论它们的致病性如何，绿色荧光蛋白+ T细胞的迁移活性、基因表达模式和向CNS的迁移是相似的。然而，专门的高致病性T细胞显着重新激活的中枢神经系统内。如果没有局部效应T细胞活化，单核细胞趋化因子的产生不足以启动和传播全面的炎症反应。弱致病性T细胞的低水平再活化不是由于无反应性，因为这些细胞可以被原位特异性抗原激活，也可以在离体分离后激活。
The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)–specific T cells in Lewis rats, whereas transfer of S100β- or myelin oligodendrocyte glycoprotein (MOG)–specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein+ T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo.
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影响因子：
8.6
作者：
Izikson, L;Klein, RS;Weiner, HL
通讯作者：
Weiner, HL
影响因子：
3.7
作者：
Glabinski, AR;Bielecki, B;Ransohoff, RM
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Ransohoff, RM
影响因子：
4.3
作者：
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LISAK, RP
DOI：
10.1084/jem.186.5.757
发表时间：
1997-08-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Germain RN
影响因子：
3.3
作者：
Adelmann, M;Wood, J;Dornmair, K
通讯作者：
Dornmair, K