Araga S, Kishimoto M, Doi S, Nakashima K
Division of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan.
J Immunol. 1999 Jul 1;163(1):476-82.
We have developed and described a new method of altering T cell-mediated autoimmune diseases by immunization with the complementary peptide against T cell epitopes. The complementary peptide (denoted NAE 07-06) to the bovine P2 protein, residues 60-70 (denoted EAN 60-70), was tested in the Lewis rat model of experimental allergic neuritis (EAN). Immunization with NAE 07-06 induced polyclonal and monoclonal Abs that inhibited the proliferation of the P2-specific T cell line, stimulated with EAN 60-70, and recognized Vbeta, but not Valpha, of TCRs. Proliferation of T cells treated with anti-NAE 07-06 Abs could be partially restored by treatment with rIL-2, in accordance with an anergy model. A homologous sequence was found between NAE 07-06 and the VDJ junction of the TCR beta-chain from an EAN 60-70-specific T cell line. Rats preimmunized with NAE 07-06 in vivo before EAN induction showed less disease severity clinically and histologically. These data suggest a new therapeutic approach for T cell-mediated autoimmune disorders through the induction of anti-TCR Abs with complementary peptide Ags.
我们已经开发并描述了一种通过用针对T细胞表位的互补肽进行免疫来改变T细胞介导的自身免疫性疾病的新方法。在实验性变应性神经炎（EAN）的Lewis大鼠模型中测试了针对牛P2蛋白第60 - 70位残基（记为EAN 60 - 70）的互补肽（记为NAE 07 - 06）。用NAE 07 - 06免疫诱导了多克隆和单克隆抗体，这些抗体抑制了用EAN 60 - 70刺激的P2特异性T细胞系的增殖，并识别TCR的Vβ而非Vα。根据无反应性模型，用抗NAE 07 - 06抗体处理的T细胞的增殖可通过用rIL - 2处理而部分恢复。在来自EAN 60 - 70特异性T细胞系的TCRβ链的VDJ连接区与NAE 07 - 06之间发现了同源序列。在EAN诱导前体内用NAE 07 - 06进行预免疫的大鼠在临床和组织学上显示出较轻的疾病严重程度。这些数据表明通过用互补肽抗原诱导抗TCR抗体为T细胞介导的自身免疫性疾病提供了一种新的治疗方法。
