Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Immunol Rev. 2011 May;241(1):89-103. doi: 10.1111/j.1600-065X.2011.01008.x.
The negative selection of self-reactive thymocytes depends on the expression of tissue-specific antigens by medullary thymic epithelial cells. The autoimmune regulator (Aire) protein plays an important role in turning on these antigens, and the absence of even one Aire-induced tissue-specific antigen in the thymus can lead to autoimmunity in the antigen-expressing target organ. Recently, Aire protein has been detected in peripheral lymphoid organs, suggesting that peripheral Aire plays a complementary role here. In these peripheral sites, Aire was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus. Furthermore, transgenic antigen expression in extrathymic Aire-expressing cells (eTACs) can mediate deletional tolerance, but the immunological relevance of Aire-dependent, endogenous tissue-specific antigens remains to be determined.
自身反应性胸腺细胞的阴性选择依赖于髓质胸腺上皮细胞表达组织特异性抗原。自身免疫调节蛋白（Aire）在开启这些抗原中发挥着重要作用，即使胸腺中仅缺少一种 Aire 诱导的组织特异性抗原，也会导致表达抗原的靶器官发生自身免疫。最近，已在周围淋巴器官中检测到 Aire 蛋白，提示外周 Aire 在此发挥着补充作用。在这些外周部位，发现 Aire 调节一组不同于在胸腺中表达的组织特异性抗原的表达。此外，在外周表达 Aire 的转基因抗原表达细胞（eTAC）中可介导删除性耐受，但 Aire 依赖性内源性组织特异性抗原的免疫学相关性仍有待确定。
