van Driel Ian R, Read Simon, Zwar Tricia D, Gleeson Paul A
The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
Curr Opin Immunol. 2005 Dec;17(6):570-6. doi: 10.1016/j.coi.2005.09.016. Epub 2005 Oct 7.
Murine autoimmune gastritis is one of the most well-defined organ-specific autoimmune diseases. CD4(+) T cells, which mediate the disease, recognize the highly abundant gastric H(+)/K(+) ATPase heterodimer. The H(+)/K(+) ATPase alpha subunit is also expressed in the thymus, in an aire-independent manner, whereas the H(+)/K(+) ATPase beta subunit is absent from the thymus. Analysis of both H(+)/K(+) ATPase-specific T cell receptor transgenic mice with different affinities for the gastric antigen and mice deficient in the H(+)/K(+) ATPase subunits has provided information on thymic and peripheral selection events. The H(+)/K(+) ATPase antigens play an important role in purging the repertoire of gastritogenic T cells, and recent data have suggested that this tolerance induction occurs primarily in the periphery. The gastritis system provides a powerful approach to determine the impact of peripheral antigen presentation in the target organ draining lymph node on tolerance and autoimmune disease.
小鼠自身免疫性胃炎是最典型的器官特异性自身免疫性疾病之一。介导该疾病的CD4(+) T细胞可识别高度丰富的胃H(+)/K(+) ATP酶异二聚体。H(+)/K(+) ATP酶α亚基也以不依赖自身免疫调节因子（AIRE）的方式在胸腺中表达，而H(+)/K(+) ATP酶β亚基在胸腺中不存在。对具有不同胃抗原亲和力的H(+)/K(+) ATP酶特异性T细胞受体转基因小鼠以及缺乏H(+)/K(+) ATP酶亚基的小鼠进行分析，提供了有关胸腺和外周选择事件的信息。H(+)/K(+) ATP酶抗原在清除致胃炎性T细胞库方面发挥重要作用，最近的数据表明这种耐受性诱导主要发生在外周。胃炎系统为确定靶器官引流淋巴结中外周抗原呈递对耐受性和自身免疫性疾病的影响提供了有力的方法。
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