Zang Ying C Q, Hong Jian, Rivera Victor M, Killian James, Zhang Jingwu Z
Multiple Sclerosis Research Unit, Department of Neurology and Baylor-Methodist Multiple Sclerosis Center, Baylor College of Medicine, Houston, TX 77030, USA.
Int Immunol. 2003 Sep;15(9):1073-80. doi: 10.1093/intimm/dxg105.
T cells recognizing myelin basic protein (MBP) are potentially involved in the pathogenesis of multiple sclerosis (MS). In vivo clonal expansion of MBP-reactive T cells in MS may relate in part to dysfunction of peripheral regulatory mechanisms, including the anti-idiotypic immune network. In this study, we examined anti-idiotypic immune responses and the functional properties of anti-idiotypic T cells in patients with MS and healthy controls using TCR peptides corresponding to a CDR3 sequence motif preferentially expressed among T cells recognizing the 83-99 immunodominant peptide of MBP in some patients with MS. The study demonstrated that anti-idiotypic T cells could be induced in vitro by 8mer and 15mer peptides containing the CDR3 motif in MS patients and healthy controls respectively. The estimated precursor frequency of the anti-idiotypic T cells was slightly reduced in MS patients compared to control subjects. The obtained anti-idiotypic T cells recognizing the 15mer TCR peptide were found to express the CD4 phenotype, produce predominantly IL-10 and inhibit the proliferation of autologous T cells recognizing the immunodominant peptide of MBP. Anti-idiotypic T cells induced by the 8mer TCR peptide were predominantly CD8+ cytotoxic T cells and exhibited cytotoxic activity against autologous MBP-specific T cells expressing the CDR3 sequence. When added in primary culture, both TCR peptides had a significant inhibitory effect on the T cell responses to the immunodominant peptide of MBP. The findings suggest that anti-idiotypic immune responses can be activated by selected TCR peptides and may play an important role in the in vivo regulation of MBP-reactive T cells.
识别髓鞘碱性蛋白（MBP）的T细胞可能参与了多发性硬化症（MS）的发病机制。MS中MBP反应性T细胞的体内克隆扩增可能部分与外周调节机制功能障碍有关，包括抗独特型免疫网络。在本研究中，我们使用与某些MS患者中识别MBP 83-99免疫显性肽的T细胞中优先表达的CDR3序列基序相对应的TCR肽，检测了MS患者和健康对照者的抗独特型免疫反应及抗独特型T细胞的功能特性。研究表明，MS患者和健康对照者分别可通过含有CDR3基序的8聚体和15聚体肽在体外诱导出抗独特型T细胞。与对照受试者相比，MS患者中抗独特型T细胞的估计前体频率略有降低。发现识别15聚体TCR肽的抗独特型T细胞表达CD4表型，主要产生IL-10，并抑制识别MBP免疫显性肽的自体T细胞的增殖。由8聚体TCR肽诱导的抗独特型T细胞主要是CD8 + 细胞毒性T细胞，并对表达CDR3序列的自体MBP特异性T细胞表现出细胞毒性活性。当添加到原代培养物中时，两种TCR肽对T细胞对MBP免疫显性肽的反应均具有显著抑制作用。这些发现表明，抗独特型免疫反应可被选定的TCR肽激活，并可能在体内对MBP反应性T细胞的调节中发挥重要作用。
