Bischof Felix, Hofmann Matthias, Schumacher Ton N M, Vyth-Dreese Florry A, Weissert Robert, Schild Hansjörg, Kruisbeek Ada M, Melms Arthur
Department of Neurology and Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
J Immunol. 2004 Mar 1;172(5):2878-84. doi: 10.4049/jimmunol.172.5.2878.
Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is primarily mediated by CD4 T cells specific for Ags in the CNS. Using MHC class II tetramers, we assessed expansion and phenotypic differentiation of polyclonal self-reactive CD4 T cells during EAE after primary and secondary challenge with the specific Ag. After EAE induction in SJL mice with proteolipid protein 139-151, CNS-specific T cells up-regulated activation markers and expanded in the draining lymph nodes and in the spleen. Less than 20% of total autoreactive T cells entered the CNS simultaneously with Th cells of other specificities. Almost all tetramer-positive cells in the CNS were activated and phenotypically distinct from the large peripheral pool. When EAE was induced in Ag-experienced mice, disease symptoms developed earlier and persisted longer; autoreactive T cells were more rapidly activated and invaded the CNS earlier. In striking contrast to specific CTLs that respond after secondary viral challenge, the absolute numbers of autoreactive CD4 T cells were not increased, indicating that the accelerated autoreactivity in Ag-experienced mice is not related to higher frequencies of autoreactive CD4 T cells.
实验性自身免疫性脑脊髓炎（EAE）是多发性硬化症的动物模型，主要由中枢神经系统中针对抗原的CD4 T细胞介导。我们使用MHC II类四聚体，评估了在用特异性抗原进行初次和二次攻击后EAE期间多克隆自身反应性CD4 T细胞的扩增和表型分化。在用蛋白脂蛋白139 - 151诱导SJL小鼠发生EAE后，中枢神经系统特异性T细胞上调激活标志物，并在引流淋巴结和脾脏中扩增。不到20%的总自身反应性T细胞与其他特异性的Th细胞同时进入中枢神经系统。中枢神经系统中几乎所有四聚体阳性细胞均被激活，且在表型上与外周大量细胞不同。当在有抗原经验的小鼠中诱导EAE时，疾病症状出现得更早且持续时间更长；自身反应性T细胞被更快地激活并更早地侵入中枢神经系统。与二次病毒攻击后反应的特异性CTL形成鲜明对比的是，自身反应性CD4 T细胞的绝对数量并未增加，这表明有抗原经验的小鼠中自身反应性加速与自身反应性CD4 T细胞的更高频率无关。
