Toh B H, van Driel I R, Gleeson P A
Department of Pathology and Immunology, Monash University Medical School, Alfred Hospital, Prahran, Victoria, Australia.
Autoimmunity. 1992;13(2):165-72. doi: 10.3109/08916939209001918.
The alpha and beta subunits of the gastric H+/K(+)-ATPase (proton pump) have been identified as the major molecular targets of parietal cell autoantibodies associated with pernicious anaemia and with murine experimental autoimmune gastritis (EAG) induced by neonatal thymectomy. Recent studies with EAG suggest that the mechanisms of peripheral tolerance and autoimmunity to extrathymic autoantigens are mediated by subsets of "regulator" and "effector" CD4+ T cells, respectively. The persistence of "effector" CD4+ autoreactive T cells in the periphery may be a direct consequence of the delayed developmental expression of the target autoantigen. We hypothesize that cytokines produced by the "regulator" T cells prevent the clonal expansion of the "effector" autoreactive T cells, and that neonatal thymectomy induces organ-specific autoimmunity in genetically susceptible individuals by the reduction of the "regulator" T cell population.
胃H⁺/K⁺-ATP酶（质子泵）的α和β亚基已被确定为与恶性贫血以及由新生期胸腺切除诱导的小鼠实验性自身免疫性胃炎（EAG）相关的壁细胞自身抗体的主要分子靶点。近期对EAG的研究表明，外周耐受和针对胸腺外自身抗原的自身免疫机制分别由“调节性”和“效应性”CD4⁺T细胞亚群介导。外周“效应性”CD4⁺自身反应性T细胞的持续存在可能是靶自身抗原发育表达延迟的直接后果。我们推测，“调节性”T细胞产生的细胞因子可阻止“效应性”自身反应性T细胞的克隆扩增，并且新生期胸腺切除通过减少“调节性”T细胞群体，在遗传易感性个体中诱导器官特异性自身免疫。
