Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs
Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs
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DOI：
10.4049/jimmunol.169.10.5415
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发表时间：
2002-11-15
影响因子：
4.4
通讯作者：
Laman, JD
中科院分区：
文献类型：
--
作者：
de Vos, AF;van Meurs, M;Laman, JD
树突状细胞被认为通过将Ags和外周信号传递到引流淋巴结（LN）来调节耐受性诱导与免疫。然而，髓鞘银是否在脱髓鞘性脑病中发生在LN中的转移和呈现尚不清楚。在这项研究中，我们证明了自身抗原在猴实验性自身免疫性脑脊髓炎（EAE）和多发性硬化症（MS）中从脑病变到颈部LN的再分布。免疫组化分析显示，与健康对照组相比，EAE猴颈LN中含有髓磷脂Ags的细胞明显增多。在表达树突状细胞/巨噬细胞特异性标记物、MHC 11类和共刺激分子的细胞中观察到髓磷脂Ags。此外，这些细胞直接与T细胞并列，表明含髓磷脂的APC和T细胞之间的同源相互作用发生在脑引流LN中。确实，髓鞘ag反应性T细胞在狨猴和恒河猴的颈部LN中被观察到。重要的是，这些发现与我们在人体组织中的发现是一致的。我们观察到，与对照组相比，MS患者LN中含有髓磷脂ag的细胞明显增多。在狨猴和恒河猴中观察到，这些细胞表达APC标记物。这些发现表明，在MS和EAE期间，T细胞对脑源性Ags的反应性调节也发生在颈LN中，而不一定发生在脑内。一个主要的暗示是，新的治疗策略可能针对外周事件，从而绕过血脑屏障。
Dendritic cells are thought to regulate tolerance induction vs immunization by transferring Ags and peripheral signals to draining lymph nodes (LN). However, whether myelin Ag transfer and presentation in LN occurs during demyelinating brain disease is unknown. In this study, we demonstrate redistribution of autoantigens from brain lesions to cervical LN in monkey experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS). Immunohistochemical analysis revealed significantly more cells containing myelin Ags in cervical LN of monkeys with EAE compared with those of healthy control monkeys. Myelin Ags were observed in cells expressing dendritic cell/macrophage-specific markers, MHC class 11, and costimulatory molecules. Moreover, these cells were directly juxtaposed to T cells, suggesting that cognate interactions between myelin-containing APC and T cells are taking place in brain-draining LN. Indeed, myelin Ag-reactive T cells were observed in cervical LN from marmosets and rhesus monkeys. Importantly, these findings were paralleled by our findings in human tissue. We observed significantly more myelin Ag-containing cells in LN of individuals with MS compared with those of control individuals. These cells expressed APC markers, as observed in marmosets and rhesus monkeys. These findings suggest that during MS and EAE, modulation of T cell reactivity against brain-derived Ags also takes place in cervical LN and not necessarily inside the brain. A major implication is that novel therapeutic strategies may be targeted to peripheral events, thereby circumventing the blood-brain barrier.