Tsuchida M, Matsumoto Y, Hirahara H, Hanawa H, Tomiyama K, Abo T
Department of Immunology, Niigata University School of Medicine, Japan.
Eur J Immunol. 1993 Oct;23(10):2399-406. doi: 10.1002/eji.1830231004.
To determine the role of encephalitogenic T cells in the formation of lesions in the central nervous system (CNS), experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by immunization with either myelin basic protein (MBP) or the synthetic peptide which corresponds to the 87-100 sequence of guinea pig MBP, and T cells expressing T cell receptor (TcR) V beta 8.2, V beta 8.5, V beta 10 and V beta 16 in the lymphoid organs and CNS were localized and quantified by flow cytometry (FCM) and immunohistochemistry. In normal rats, the percentage of T cells expressing these V beta phenotypes to the total number of TcR alpha beta+ T cells, as determined by FCM, ranged from 5% to 10% in the lymph node. V beta 16+ T cells were the most predominant population among the four V beta subsets tested. Essentially the same findings were obtained from the analysis of the lymphoid organs of rats with EAE which had been induced by immunization with the same two antigens. In sharp contrast, 15-20% of the T cells isolated from lesions of MBP-induced EAE expressed V beta 8.2. Thus, the percentage of V beta 8.2+ T cells in the EAE lesions was threefold higher than that in the lymph node, while the proportions of V beta 8.5+, V beta 10+ and V beta 16+ T cells were about the same in both organs. The predominance of V beta 8.2+ T cells in EAE lesions was confirmed by counts of immunohistochemically stained T cells in the spinal cord. Moreover, it was revealed that (i) the predominance of V beta 8.2+ T cells was greatest during the development of EAE and became less obvious at the recovery state, and (ii) at the peak stage of EAE, approximately 85% of V beta 8.2+ T cells were distributed in the parenchyma while 15% were in the perivascular space of the CNS vessels. These findings indicate that encephalitogenic T cells which express V beta 8.2 infiltrate the CNS at a very early stage of EAE and become the predominant population in infiltrating T cells, and further suggest that encephalitogenic T cells, not only recruit inflammatory cells in the CNS, but also cause neural tissue damage, such as demyelination.
为了确定致脑炎性T细胞在中枢神经系统（CNS）病变形成中的作用，通过用髓鞘碱性蛋白（MBP）或与豚鼠MBP的87 - 100序列相对应的合成肽免疫，在Lewis大鼠中诱导实验性自身免疫性脑脊髓炎（EAE），并通过流式细胞术（FCM）和免疫组织化学对淋巴器官和CNS中表达T细胞受体（TcR）Vβ8.2、Vβ8.5、Vβ10和Vβ16的T细胞进行定位和定量。在正常大鼠中，通过FCM测定，表达这些Vβ表型的T细胞占TcRαβ + T细胞总数的百分比在淋巴结中为5%至10%。在测试的四个Vβ亚群中，Vβ16 + T细胞是最主要的群体。在用相同的两种抗原免疫诱导的EAE大鼠的淋巴器官分析中也得到了基本相同的结果。与之形成鲜明对比的是，从MBP诱导的EAE病变中分离出的T细胞中有15% - 20%表达Vβ8.2。因此，EAE病变中Vβ8.2 + T细胞的百分比比淋巴结中的高三倍，而Vβ8.5 +、Vβ10 +和Vβ16 + T细胞在两个器官中的比例大致相同。通过对脊髓中免疫组织化学染色的T细胞计数，证实了EAE病变中Vβ8.2 + T细胞的优势。此外，还发现：（i）Vβ8.2 + T细胞的优势在EAE发展过程中最大，在恢复状态时不太明显；（ii）在EAE的高峰期，大约85%的Vβ8.2 + T细胞分布在实质中，15%分布在CNS血管的血管周围间隙中。这些发现表明，表达Vβ8.2的致脑炎性T细胞在EAE的非常早期阶段就浸润到CNS中，并成为浸润T细胞中的主要群体，进一步表明致脑炎性T细胞不仅在CNS中募集炎性细胞，还会导致神经组织损伤，如脱髓鞘。
