Haque M A, Kimoto M, Inada S, Tokunaga O, Kohashi O
Department of Microbiology, Saga Medical School, Nabeshima, Saga, Japan.
Immunology. 1998 Aug;94(4):536-42. doi: 10.1046/j.1365-2567.1998.00543.x.
Studies suggested that experimental autoimmune diseases can effectively be prevented and treated by application of normal autoreactive T cells or autoreactive T cells in an attenuated form. In this study, several autoreactive CD4- CD8- T-cell clones (A2, A6, and A13 cells) were isolated for the first time from the draining lymph nodes of Lewis rats with adjuvant arthritis (AA). Surprisingly, intraperitoneal inoculation with A13 cells, but not A2 or A6 cells protected rats from AA both clinically and histologically. It was demonstrated that A13 cells were CD4- CD8- alpha beta T cells, and showed proliferative responses to irradiated syngeneic spleen cells (antigen-presenting cells; APC). Interestingly, A13 cells proliferated against concanavalin A (Con A) and staphylococcal enterotoxin B (SEB), but did not show any proliferation to Mycobacterium tuberculosis (Mt), or its 65 000 MW heat-shock protein (HSP). Rats protected from AA by inoculation with A13 cells showed a specific anti-idiotypic delayed-type hypersensitivity reaction compared with other autoreactive T cells (A2 or A6 cells). These findings demonstrate that AA can be suppressed by autoreactive CD4- CD8- alpha beta T cells, and these cells may be used as therapeutic agents in experimental autoimmunity.
研究表明,应用正常的自身反应性T细胞或以减毒形式存在的自身反应性T细胞能够有效预防和治疗实验性自身免疫性疾病。在本研究中,首次从患有佐剂性关节炎(AA)的Lewis大鼠引流淋巴结中分离出几种自身反应性CD4-CD8-T细胞克隆(A2、A6和A13细胞)。令人惊讶的是,腹腔注射A13细胞而非A2或A6细胞可在临床和组织学上保护大鼠免受AA侵害。结果表明,A13细胞是CD4-CD8-αβT细胞,对经辐照的同基因脾细胞(抗原呈递细胞;APC)表现出增殖反应。有趣的是,A13细胞针对刀豆球蛋白A(Con A)和葡萄球菌肠毒素B(SEB)发生增殖,但对结核分枝杆菌(Mt)或其65000 MW热休克蛋白(HSP)未表现出任何增殖。与其他自身反应性T细胞(A2或A6细胞)相比,接种A13细胞而免受AA侵害的大鼠表现出特异性抗独特型迟发型超敏反应。这些发现表明,AA可被自身反应性CD4-CD8-αβT细胞抑制,并且这些细胞可作为实验性自身免疫中的治疗剂。