Nishio A, Hosono M, Watanabe Y, Sakai M, Okuma M, Masuda T
First Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Gastroenterology. 1994 Nov;107(5):1408-14. doi: 10.1016/0016-5085(94)90543-6.
BACKGROUND/AIMS: H+,K(+)-adenosine triphosphatase (H+,K(+)-ATPase) of parietal cells is an organ-specific enzyme recognized by autoantibodies found in human and murine autoimmune gastritis (AIG). Murine AIG can be induced in BALB/c mice by thymectomy 3 days after birth and is a T cell-mediated disease. This study examined the specificity of T cells that cause AIG and the role of H+,K(+)-ATPase in this disease.
From an AIG mouse, a gastritogenic T-cell clone (II-6) was established, and its reactivity to synthetic peptides of H+,K(+)-ATPase was tested.
II-6 cells are CD4+, V beta 14+, and interferon gamma producers. Adoptive transfer of II-6 cells to syngeneic nude mice resulted in AIG without the production of autoantibodies to parietal cells. The II-6 cells were responsive not only to murine but also to human and porcine parietal cells. Their proliferation was also induced by amino acids 891-905 (alpha 891) and 892-906 (alpha 892) of the alpha subunit of porcine and human H+,K(+)-ATPase, respectively.
The T-cell response to a single epitope of H+,K(+)-ATPase, the amino acid sequence of which is conserved among at least three mammals tested, is sufficient to cause AIG. Autoantibodies to parietal cells are not detected in these AIG mice.
背景/目的:壁细胞的H⁺,K⁺ - 腺苷三磷酸酶(H⁺,K⁺ - ATP酶)是一种器官特异性酶,可被人类和小鼠自身免疫性胃炎(AIG)中发现的自身抗体识别。出生后3天进行胸腺切除术可在BALB/c小鼠中诱导出小鼠AIG,这是一种T细胞介导的疾病。本研究检测了导致AIG的T细胞的特异性以及H⁺,K⁺ - ATP酶在该疾病中的作用。
从一只AIG小鼠中建立了一个致胃炎性T细胞克隆(II - 6),并测试了其对H⁺,K⁺ - ATP酶合成肽的反应性。
II - 6细胞为CD4⁺、Vβ14⁺且产生干扰素γ。将II - 6细胞过继转移至同基因裸鼠可导致AIG,且不产生针对壁细胞的自身抗体。II - 6细胞不仅对小鼠壁细胞有反应,对人和猪的壁细胞也有反应。它们的增殖还分别由猪和人H⁺,K⁺ - ATP酶α亚基的氨基酸891 - 905(α891)和892 - 906(α892)诱导。
对H⁺,K⁺ - ATP酶单个表位的T细胞反应足以导致AIG,该表位的氨基酸序列在至少三种受试哺乳动物中保守。在这些AIG小鼠中未检测到针对壁细胞的自身抗体。