滤泡辅助性T细胞在实验性自身免疫性脑脊髓炎发病过程中的作用

Mechanism of T follicular cells in experimental autoimmune encephalomyelitis

目的:探讨滤泡辅助性T细胞在实验性自身免疫性脑脊髓炎中的作用机制。方法:随机将C57BL/6小鼠分为CFA组、EAE组、anti-ICOSL组和control组。用流式细胞术检测不同时间点Tfh细胞的变化及T细胞的活化情况,石蜡切片染色观察炎细胞浸润、脱髓鞘及生发中心的改变,ELISA法检测髓鞘蛋白特异性抗体的分泌水平。结果:anti-ICOSL治疗组较EAE对照组临床评分低(P<0.05),炎症浸润减轻,无脱髓鞘病变,Tfh细胞比例降低,但活性不受影响,不能够形成生发中心,并且髓鞘蛋白特异性抗体的分泌减少。结论:滤泡辅助性T细胞通过与B细胞的相互作用促进生发中心形成,分泌抗神经髓鞘蛋白MOG35-55特异性抗体发挥致病性作用。

Objective： To evaluate the mechanism of T follicular helper cells （ Tfh ） in experimental autoimmune encephalomyelitis （EAE） via in vivo experiments. Methods：C57BL/6 mice were randomly divided into four groups,CFA group,EAE group,anti-ICOSL group and control group. Lymphocytes of different time points isolated from draining lymph nodes and spleen were stained for T follicular helper cells surface marker and T cells activation surface marker and analyzed by FACS. Observed parameters include inflammatory infiltration,demyelination in spinal cord and germinal center in spleen. ELISA was used to measure the level of antigen specific antibodies. Results： Mice in anti-ICOSL treated group developed mild disease was with lower clinical scores when compared with the EAE group. HE staining results turned out with alleviated inflammation and Luxol Fast Blue staining（ LFB） showed no demyelization in anti-ICOSL treated mice compared with non-treated EAE models. Flow cytometry results revealed that percentages of T follicular helper cells decreased though the whole activated degree T cells was not influenced in anti-ICOSL treated group. Fewer ger minal center was found in both anti-ICOSL group and CFA group with reduced secretion of MOG-specific Ab. Conclusion：T follicular helper cells supported the development of cognate B cells,promoted the formation of germinal center,facilitate pathogenic MOG-specific Ab secretion,thus enhance EAE.