Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response
Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response
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DOI：
10.1007/s00401-012-1023-3
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发表时间：
2012-12-01
影响因子：
12.7
通讯作者：
Lehmann, Paul V.
中科院分区：
文献类型：
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作者：
Kuerten, Stefanie;Schickel, Achim;Lehmann, Paul V.
虽然 T 细胞在多发性硬化症 (MS) 中的作用已得到广泛研究，但 B 细胞的致病作用直到最近才引起了人们的广泛关注，当时有研究表明，B 细胞聚集体可以在 MS 患者亚群的脑膜中形成，并被认为与该患者群体中的晚期和更具侵袭性的疾病相关。然而，这些聚集体是否确实存在随后受到质疑，其功能意义仍不清楚。在这里，我们研究了髓鞘碱性蛋白（MBP）-蛋白脂质蛋白（PLP）诱导的实验性自身免疫性脑脊髓炎（EAE），这是少数依赖于 B 细胞的多发性硬化症动物模型之一。我们提供的证据表明，在 MBP-PLP 引发的 EAE 中，B 细胞聚集反映了中枢神经系统 (CNS) 中的淋巴新生。疾病发作几天后，B 细胞聚集就已经存在。随着疾病进展，中枢神经系统 B 细胞聚集体越来越多地表现出三级淋巴器官 (TLO) 的表型。我们的结果进一步表明，这些 TLO 不仅仅是疾病的附带现象，而且具有功能活性，支持髓磷脂特异性 T 细胞反应的鞘内决定性扩散。我们的数据表明，中枢神经系统不是一个被动的“免疫特权”靶器官，而是一个隔室，其中高度活跃的免疫反应可以延续和放大自身免疫病理，从而自主地促进疾病进展。
While the role of T cells has been studied extensively in multiple sclerosis (MS), the pathogenic contribution of B cells has only recently attracted major attention, when it was shown that B cell aggregates can develop in the meninges of a subset of MS patients and were suggested to be correlates of late-stage and more aggressive disease in this patient population. However, whether these aggregates actually exist has subsequently been questioned and their functional significance has remained unclear. Here, we studied myelin basic protein (MBP)-proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE), which is one of the few animal models for MS that is dependent on B cells. We provide evidence that B cell aggregation is reflective of lymphoid neogenesis in the central nervous system (CNS) in MBP-PLP-elicited EAE. B cell aggregation was present already few days after disease onset. With disease progression CNS B cell aggregates increasingly displayed the phenotype of tertiary lymphoid organs (TLOs). Our results further imply that these TLOs were not merely epiphenomena of the disease, but functionally active, supporting intrathecal determinant spreading of the myelin-specific T cell response. Our data suggest that the CNS is not a passive "immune-privileged" target organ, but rather a compartment, in which highly active immune responses can perpetuate and amplify the autoimmune pathology and thereby autonomously contribute to disease progression.