The immunopathology of acute experimental allergic encephalomyelitis induced with myelin proteolipid protein. T cell receptors in inflammatory lesions.
The immunopathology of acute experimental allergic encephalomyelitis induced with myelin proteolipid protein. T cell receptors in inflammatory lesions.
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DOI：
10.4049/jimmunol.149.4.1444
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发表时间：
1992-08
影响因子：
4.4
通讯作者：
Raymond A. Sobel;Vijay K. Kuchroo
中科院分区：
文献类型：
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作者：
Raymond A. Sobel;Vijay K. Kuchroo
为了确定在自身免疫性疾病模型的炎性病变中是否存在表达特定TCR Vβ链的T细胞占优势，对实验性变态反应性脑脊髓炎(EAE)小鼠中枢神经系统(CNS)组织中TCR的表达进行了分析。用与髓鞘蛋白脂蛋白139-151残基对应的合成肽致敏或过继转移髓鞘蛋白脂蛋白139-151特异性脑源性T细胞克隆诱导SJL/J小鼠急性EAE。当小鼠出现EAE临床症状时，或在致敏或T细胞转移后40天内，小鼠被处死。用一组抗T细胞标志物的单抗对低温恒温器、中枢神经系统和淋巴组织切片进行免疫组织化学染色，并计数炎症灶中染色细胞的比例。在主动诱导和过继转移的EAE小鼠中，浸润物由许多CD3+、TCRαβ+和CD4+细胞组成，较少的CD8+细胞和少量TCR Gamma Delta+细胞。炎症灶中CD45+白细胞中约30%为T细胞。TCR Vβ2、3、4、6、7和14在浸润液中均有表达，而在SJL小鼠中缺失的TCR Vβ8和11未见表达。当通过转移使用Vβ2、6、10或17的T细胞克隆来诱导EAE时，皮损中也有T细胞的异质性聚集。在EAE皮损和小鼠的脾中也检测到类似比例的TCR Vβ+和Gamma Delta+细胞。因此，当急性EAE出现临床症状时，在中枢神经系统病变中发现外周来源的异质TCR Vβ+细胞，即使当免疫应答是由短肽Ag或由使用单个TCR Vβ的T细胞克隆启动时也是如此。
To determine whether there is predominance of T cells expressing a particular TCR V beta chain in the inflammatory lesions of an autoimmune disease model, TCR expression was analyzed in central nervous system (CNS) tissues of mice with experimental allergic encephalomyelitis (EAE). Acute EAE was induced in SJL/J mice either by sensitization with a synthetic peptide corresponding to myelin proteolipid protein residues 139-151 or by adoptive transfer of myelin proteolipid protein peptide 139-151-specific encephalitogenic T cell clones. Mice were killed when they showed clinical signs of EAE or by 40 days after sensitization or T cell transfer. Cryostat CNS and lymphoid tissue sections were immunostained with a panel of mAb to T cell markers and proportions of stained cells were counted in inflammatory foci. In mice with both actively induced and adoptively transferred EAE, infiltrates consisted of many CD3+, TCR alpha beta+, and CD4+ cells, fewer CD8+ cells, and small numbers of TCR gamma delta+ cells. Approximately 30% of CD45+ leukocytes in the inflammatory foci were T cells. Cells expressing TCR V beta 2, 3, 4, 6, 7 and 14 were detected in the infiltrates, whereas TCR V beta 8 and 11, which that are deleted in SJL mice, were absent. When EAE was induced by transfer of T cell clones that use either V beta 2, 6, 10, or 17, there was also a heterogeneous accumulation of T cells in the lesions. Similar proportions of TCR V beta+ and gamma delta+ cells were detected in EAE lesions and in the spleens of the mice. Thus, at the time that clinical signs are present in acute EAE, peripherally derived, heterogeneous TCR V beta+ cells are found in CNS lesions, even when the immune response is initiated to a short peptide Ag or by a T cell clone using a single TCR V beta.