Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Curr Opin Immunol. 2011 Apr;23(2):198-206. doi: 10.1016/j.coi.2010.11.007. Epub 2010 Dec 14.
In the thymus, developing T cells that react against self-antigens with high affinity are deleted in the process of negative selection. An essential component of this process is the display of self-antigens, including those whose expression are usually restricted to specific tissues, to developing T cells within the thymus. The Autoimmune Regulator (Aire) gene plays a crucial role in the expression of tissue specific self-antigens within the thymus, and disruption of Aire function results in spontaneous autoimmunity in both humans and mice. Recent advances have been made in our understanding of how Aire influences the expression of thousands of tissue-specific antigens in the thymus. Additional roles of Aire, including roles in chemokine and cytokine expression, have also been revealed. Factors important in the differentiation of Aire-expressing medullary thymic epithelial cells have been defined. Finally, the identity of antigen presenting cells in negative selection, including the role of medullary thymic epithelial cells in displaying tissue specific antigens to T cells, has also been clarified.
在胸腺中，与自身抗原反应具有高亲和力的发育中的 T 细胞在负选择过程中被删除。这个过程的一个重要组成部分是将自身抗原（包括那些通常仅限于特定组织表达的抗原）呈递给胸腺内的发育中的 T 细胞。自身免疫调节因子（Aire）基因在胸腺内组织特异性自身抗原的表达中起着至关重要的作用，Aire 功能的破坏会导致人类和小鼠自发性自身免疫。最近，我们对 Aire 如何影响胸腺中数千种组织特异性抗原的表达有了更多的了解。Aire 的其他作用，包括对趋化因子和细胞因子表达的作用，也已经被揭示。Aire 表达的髓质胸腺上皮细胞分化的重要因素也已被定义。最后，负选择中抗原呈递细胞的身份，包括髓质胸腺上皮细胞在向 T 细胞展示组织特异性抗原方面的作用，也已经得到阐明。
