Scarff K J, Pettitt J M, Van Driel I R, Gleeson P A, Toh B H
Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia.
Immunology. 1997 Sep;92(1):91-8. doi: 10.1046/j.1365-2567.1997.00302.x.
The gastric H+/K(+)-ATPase has been implicated as a major autoantigen in pernicious anaemia in humans and in thymectomy-induced autoimmune gastritis in mice. Here we have shown that autoimmune gastritis can be generated by direct immunization of non-thymectomized BALB/c mice with mouse gastric H+/K(+)-ATPase in complete Freund's adjuvant. The gastritis was characterized by infiltration of the gastric submucosa and mucosa with macrophages, CD4+ and CD8+ T cells, and B cells and by circulating autoantibodies to the H+/K(+)-ATPase. The mononuclear infiltrate within the gastric mucosa was accompanied by loss of parietal and zymogenic cells and accumulation of small immature epithelial cells. Splenocytes from gastritic mice adoptively transferred gastritis to naive recipients. Cessation of immunization resulted in decrease in autoantibody titre and regeneration of parietal and zymogenic cells. The results directly confirm that the gastric H+/K(+)-ATPase is the causative autoantigen in the genesis of autoimmune gastritis. Recovery of the lesion following cessation of immunization suggests that homeostatic mechanisms can reverse a destructive autoimmune process.
胃H⁺/K⁺-ATP酶被认为是人类恶性贫血以及小鼠胸腺切除诱导的自身免疫性胃炎中的主要自身抗原。在此我们表明，通过用完全弗氏佐剂中的小鼠胃H⁺/K⁺-ATP酶直接免疫未进行胸腺切除的BALB/c小鼠，可引发自身免疫性胃炎。该胃炎的特征是胃黏膜下层和黏膜有巨噬细胞、CD4⁺和CD8⁺T细胞以及B细胞浸润，并有针对H⁺/K⁺-ATP酶的循环自身抗体。胃黏膜内的单核细胞浸润伴随着壁细胞和泌酸细胞的丧失以及小的未成熟上皮细胞的积聚。来自患胃炎小鼠的脾细胞将胃炎过继转移给未接触过抗原的受体。停止免疫导致自身抗体滴度下降以及壁细胞和泌酸细胞再生。这些结果直接证实胃H⁺/K⁺-ATP酶是自身免疫性胃炎发生过程中的致病性自身抗原。停止免疫后病变的恢复表明稳态机制可逆转破坏性的自身免疫过程。
