Inconsistence between number and function of autoreactive T cells in the course of experimental autoimmune encephalomyelitis
Inconsistence between number and function of autoreactive T cells in the course of experimental autoimmune encephalomyelitis
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实验性自身免疫性脑脊髓炎病程中自身反应性T细胞数量与功能的不一致
DOI：
10.1080/08820139.2017.1367008
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发表时间：
2018-01
影响因子：
2.8
通讯作者：
Chuanlai Shen
中科院分区：
文献类型：
--
作者：
Xin Wan;Weiya Pei;Yiming Zhang;Lei Zhang;Khawar Ali Shahzad;Tao Xu;Chuanlai Shen
摘要背景：小鼠实验性自身免疫性脑脊髓炎（EAE）是广泛使用的多发性硬化（MS）模型。自身反应性CD 4+和CD 8 + T细胞在小鼠EAE发展中的作用已得到证实。然而，髓鞘抗原反应性CD 4+和CD 8 + T细胞在次级淋巴器官中的频率和反应性之间的关系及其与CNS炎症和病理损伤的关系在EAE小鼠模型的过程中的信息很少。研究方法：本研究通过髓鞘少突胶质细胞蛋白（MOG）35-55肽免疫C57 BL/6 J小鼠，建立了临床病程包含急性发作、高峰和慢性缓解阶段的EAE模型，并监测了临床和病理参数以及病程不同阶段的自身反应性T细胞。结果如下：脑和脊髓中炎性浸润、髓鞘丢失和星形胶质细胞增殖的动态变化与EAE过程中观察到的临床严重程度高度一致。然而，次级淋巴器官中MOG特异性CD 4+和CD 8 + T细胞的频率与MOG反应性T细胞产生IFN-γ的动态趋势不同。同时，MOG反应性CD 4 + T细胞的IL-17产生与MOG特异性CD 4 + T细胞的增殖一致。结论：在EAE早期，CD 4+和CD 8 + T细胞对MOG抗原刺激产生IFN-γ最敏感，但在高峰期和后期，尽管CD 4+和CD 8 + T细胞增殖旺盛，但很快就丧失了产生IFN-γ的功能。
ABSTRACT Background: Mouse experimental autoimmune encephalomyelitis (EAE) is widely used model of multiple sclerosis (MS). The role of autoreactive CD4+ and CD8+ T cells in the development of mouse EAE has been demonstrated. However, little information is available about the relation between the frequency and reactivity of myelin antigen-reactive CD4+ and CD8+ T cells in secondary lymphoid organs and their relevance with the inflammation and pathological lesion of CNS during the course of EAE mouse model. Methods: In this study, an EAE model with a clinical course containing acute onset, peak and chronic remission stages was established in C57BL/6J mice by myelin oligodendrocyte protein (MOG)35–55 peptide immunization, and followed by the monitoring of clinical and pathological parameters and autoreactive T cells at different stages during the course. Results: The dynamic changes of inflammatory infiltration, myelin loss, and astrocyte proliferation in brain and spinal cord were highly consistent with clinical severity observed in EAE course. However, the frequencies of both MOG-specific CD4+ and CD8+ T cells in secondary lymphoid organs presented different dynamic trends from the IFN-γ production by MOG-reactive T cells. Meanwhile, the IL-17 production by MOG-reactive CD4+ T cells was consistent with the proliferation of MOG-specific CD4+ T cells. Conclusions: Both CD4+ and CD8+ T cells were most sensitive to MOG antigen stimulation for IFN-γ production during the early stage of EAE, but then rapidly lost the function despite their vigorous proliferation at the peak stage and later.
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影响因子：
4.4
作者：
C. Radu;S. Anderton;Mihail Firan;D. Wraith;E. Ward
通讯作者：
C. Radu;S. Anderton;Mihail Firan;D. Wraith;E. Ward
影响因子：
82.9
作者：
Rangachari, Manu;Zhu, Chen;Sakuishi, Kaori;Xiao, Sheng;Karman, Jozsef;Chen, Andrew;Angin, Mathieu;Wakeham, Andrew;Greenfield, Edward A.;Sobel, Raymond A.;Okada, Hitoshi;McKinnon, Peter J.;Mak, Tak W.;Addo, Marylyn M.;Anderson, Ana C.;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
4.3
作者：
Hofstetter, HH;Ibrahim, SM;Gold, R
通讯作者：
Gold, R
影响因子：
4.4
作者：
Hofstetter, HH;Shive, CL;Forsthuber, TG
通讯作者：
Forsthuber, TG
DOI：
10.3791/51275
发表时间：
2014-04-15
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Bittner S;Afzali AM;Wiendl H;Meuth SG
通讯作者：
Meuth SG