Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.
Sci Rep. 2020 Nov 24;10(1):20485. doi: 10.1038/s41598-020-77588-9.
Beyond the major role of T cells in the pathogenesis of the autoimmune neuroinflammatory disorder multiple sclerosis (MS), recent studies have highlighted the impact of B cells on pathogenic inflammatory processes. Follicular T helper cells (Tfh) are essential for the promotion of B cell-driven immune responses. However, their role in MS and its murine model, experimental autoimmune encephalomyelitis (EAE), is poorly investigated. A first step to achieving a better understanding of the contribution of Tfh cells to the disease is the consideration of Tfh cell localization in relation to genetic background and EAE induction method. Here, we investigated the Tfh cell distribution during disease progression in disease relevant organs in three different EAE models. An increase of Tfh frequency in the central nervous system (CNS) was observed during peak of C57BL/6 J EAE, paralleling chronic disease activity, whereas in relapsing-remitting SJL EAE mice Tfh cell frequencies were increased during remission. Furthermore, transferred Tfh-skewed cells polarized in vitro induced mild clinical symptoms in B6.Rag1 mice. We identified significantly higher levels of Tfh cells in the dura mater than in the CNS both in C57BL/6 and in SJL/J mice. Overall, our study emphasizes diverse, non-static roles of Tfh cells during autoimmune neuroinflammation.
除了 T 细胞在自身免疫性神经炎症性疾病多发性硬化症 (MS) 的发病机制中起主要作用外，最近的研究还强调了 B 细胞对致病炎症过程的影响。滤泡辅助性 T 细胞 (Tfh) 是促进 B 细胞驱动的免疫反应所必需的。然而，它们在 MS 及其小鼠模型实验性自身免疫性脑脊髓炎 (EAE) 中的作用尚未得到充分研究。更好地了解 Tfh 细胞对疾病的贡献的第一步是考虑 Tfh 细胞在与遗传背景和 EAE 诱导方法相关的疾病中的定位。在这里，我们在三种不同的 EAE 模型中研究了疾病相关器官中疾病进展过程中的 Tfh 细胞分布。在 C57BL/6 J EAE 的高峰期观察到中枢神经系统 (CNS) 中 Tfh 频率增加，与慢性疾病活动平行，而在复发缓解型 SJL EAE 小鼠中，Tfh 细胞频率在缓解期增加。此外，体外极化的转移 Tfh 偏向细胞在 B6.Rag1 小鼠中诱导了轻微的临床症状。我们发现 C57BL/6 和 SJL/J 小鼠的硬脑膜中 Tfh 细胞水平明显高于 CNS。总的来说，我们的研究强调了 Tfh 细胞在自身免疫性神经炎症中的多样化、非静态作用。
