调节T细胞和1型糖尿病

Regulatory T cells and Type 1 diabetes

1型糖尿病是一种T细胞介导的胰岛β细胞进行性损伤的自身免疫病。在自身免疫过程中不仅有自身反应性T细胞的参与,也有可抑制免疫反应的自身反应调节性T细胞(Tregs)的参与,因而提高Tregs的反应性抑制自身免疫从而治疗糖尿病是很有希望的治疗策略。Tregs存在不同类型,它们的作用方式和表型还需进一步界定。其中抗原特异的诱导型Tregs可以在病变器官内发挥作用,通过细胞因子介导的“抑制旁观者”机制不依赖于抗原特异性地抑制自身反应性T细胞。而无抗原特异性的自然生成CD4+CD25+Tregs的应用将导致全身性的免疫调节和抑制,可能更适用于全身性而非器官特异性的自身免疫紊乱。因此应用抗原特异的诱导型Tregs治疗1型糖尿病可能更可取,但其成功尚有赖于对其最适诱导抗原、精确表型及体内作用机制的进一步了解。

Type 1 diabetes is a T-cell-mediated autoimmune disease, resulting in destruction of the insulin-producing beta ceils in the pancreas. However, recent evidence shows that autoimmune processes are composed not only of autoaggressive T-cell responses but also of autoreactive regulatory components. Enhancing regulatory T-cell （Treg） responses, therefore, has become an area of intense focus as a means treating autoimmune diseases like Type 1 diabetes. It is clear that different subsets of regula tory T-cells exist, and their mode of action and phenotype will need to be further characterized. In particular, antigen-specific regulatory T-cells may be useful owing to their ability to act within the affected tissue and suppress autoaggressive T-cells independent of antigen specificity as bystander suppressors in a cytokine-dependent manner. Thus, one can indeed envision autologous Treg therapy in the not too distant future. Application of universal Treg therapy without antigen specificity will lead to systemic immune modulation and suppression, which might be suitable for some systemic but not organ-specific autoimmune disorders. Therefore, antigen-specific induction of Tregs might be preferable - success will be highly dependent on understanding the in vivo set points and precise phenotype of the ＇ best＇ antigen-specific Treg for a given disease.