Institut National de la Santé et de la Recherche Médicale, Toulouse, France.
Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12437-42. doi: 10.1073/pnas.1107136108. Epub 2011 Jul 11.
Mutations in the gene encoding the transcription factor autoimmune regulator (AIRE) are responsible for autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome. AIRE directs expression of tissue-restricted antigens in the thymic medulla and in lymph node stromal cells and thereby substantially contributes to induction of immunological tolerance to self-antigens. Data from experimental mouse models showed that AIRE deficiency leads to impaired deletion of autospecific T-cell precursors. However, a potential role for AIRE in the function of regulatory T-cell populations, which are known to play a central role in prevention of immunopathology, has remained elusive. Regulatory T cells of CD8(+)CD28(low) phenotype efficiently control immune responses in experimental autoimmune and colitis models in mice. Here we show that CD8(+)CD28(low) regulatory T lymphocytes from AIRE-deficient mice are transcriptionally and phenotypically normal and exert efficient suppression of in vitro immune responses, but completely fail to prevent experimental colitis in vivo. Our data therefore demonstrate that AIRE plays an important role in the in vivo function of a naturally occurring regulatory T-cell population.
基因突变转录因子自身免疫调节因子（AIRE）负责自身免疫性多内分泌腺病念珠菌病外胚层营养不良综合征。AIRE 指导组织特异性抗原在胸腺髓质和淋巴结基质细胞中的表达，从而大大有助于诱导对自身抗原的免疫耐受。来自实验小鼠模型的数据表明，AIRE 缺乏导致自身特异性 T 细胞前体的删除受损。然而，AIRE 在调节性 T 细胞群体功能中的潜在作用，众所周知，调节性 T 细胞在预防免疫病理学中起着核心作用，仍然难以捉摸。CD8(+)CD28(low)表型的调节性 T 细胞在实验性自身免疫和结肠炎模型中有效地控制免疫反应。在这里，我们表明，来自 AIRE 缺陷小鼠的 CD8(+)CD28(low)调节性 T 淋巴细胞在转录和表型上是正常的，并有效地抑制体外免疫反应，但完全不能预防体内实验性结肠炎。因此，我们的数据表明，AIRE 在天然存在的调节性 T 细胞群体的体内功能中起着重要作用。
