Division of Allergy and Immunology, Department of Pediatrics, Medical College of Wisconsin and Children's Research Institute, Milwaukee, WI 53226, USA.
J Immunol. 2010 Aug 15;185(4):2147-56. doi: 10.4049/jimmunol.1000136. Epub 2010 Jul 16.
The importance of regulatory T cells in immune tolerance is illustrated by the human immune dysregulatory disorder IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked), caused by a lack of regulatory T cells due to decreased or absent expression of Foxp3. Although the majority of work on regulatory T cells has focused on their ability to suppress T cell responses, the development of significant autoantibody titers in patients with IPEX suggests that regulatory T cells also contribute to the suppression of autoreactive B cells. Using a murine model, deficient in the expression of Foxp3, we show that B cell development is significantly altered in the absence of regulatory T cells. Furthermore, we identify a loss of B cell anergy as a likely mechanism to explain the production of autoantibodies that occurs in the absence of regulatory T cells. Our results suggest that regulatory T cells, by either direct or indirect mechanisms, modulate B cell development and anergy.
调节性 T 细胞在免疫耐受中的重要性，通过人类免疫失调疾病 IPEX（免疫失调、多内分泌腺病、肠病、X 连锁）得到说明，其原因是由于 Foxp3 表达减少或缺失，导致调节性 T 细胞缺乏。尽管大多数关于调节性 T 细胞的研究都集中在它们抑制 T 细胞反应的能力上，但 IPEX 患者中出现显著的自身抗体滴度表明，调节性 T 细胞也有助于抑制自身反应性 B 细胞。使用缺乏 Foxp3 表达的小鼠模型，我们表明在缺乏调节性 T 细胞的情况下，B 细胞的发育会发生显著改变。此外，我们确定 B 细胞失能的丧失可能是一种解释在缺乏调节性 T 细胞时发生的自身抗体产生的机制。我们的结果表明，调节性 T 细胞通过直接或间接的机制调节 B 细胞的发育和失能。
