Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Mucosal Immunol. 2010 May;3(3):216-29. doi: 10.1038/mi.2010.4. Epub 2010 Feb 17.
That regulatory T cells (Tregs) have a crucial role in controlling allergic diseases such as asthma is now undisputed. The cytokines most commonly implicated in Treg-mediated suppression of allergic asthma are transforming growth factor-beta (TGF-beta) and interleukin (IL)-10). In addition to naturally occurring Tregs, adaptive Tregs, induced in response to foreign antigens, have been shown in recent studies. The concept of inducible/adaptive Tregs (iTregs) has considerable significance in preventing asthma if generated early enough in life. This is because cytokines such as IL-4 and IL-6 inhibit Foxp3 induction in naive CD4+ T cells and therefore de novo generation of Tregs can be expected to be less efficient when it is concomitant with effector cell development in response to an allergen. However, if iTregs can be induced, the process of infectious tolerance would facilitate expansion of the iTreg pool as suggested in the recent literature. It is tempting to speculate that there is a window of opportunity in early life in the context of a relatively immature immune system that is permissive for the generation of iTregs specific to a spectrum of allergens that would regulate asthma for lifelong. The focus of this review is the relevance of nTregs and iTregs in controlling asthma from early life into adulthood, the mechanisms underlying Treg function, and the prospects for using our current concepts to harness the full potential of Tregs to limit disease development and progression.
现在已经毫无疑问，调节性 T 细胞（Tregs）在控制哮喘等过敏性疾病方面发挥着关键作用。最常涉及 Treg 介导的过敏性哮喘抑制的细胞因子是转化生长因子-β（TGF-β）和白细胞介素（IL）-10。除了天然存在的 Tregs 外，最近的研究还表明，对外来抗原的反应诱导适应性 Tregs。在诱导/适应性 Tregs（iTregs）的概念中，如果在生命早期产生足够早，对预防哮喘具有重要意义。这是因为细胞因子（如 IL-4 和 IL-6）抑制幼稚 CD4+T 细胞中 Foxp3 的诱导，因此当与对过敏原的效应细胞发育同时发生时，预期新生成的 Tregs 的效率会降低。然而，如果可以诱导 iTregs，则正如最近文献中所建议的那样，感染耐受过程将有利于 iTreg 池的扩张。人们不禁推测，在相对不成熟的免疫系统的背景下，生命早期存在一个机会窗口，有利于针对一系列过敏原生成 iTregs，从而调节终生的哮喘。这篇综述的重点是 nTregs 和 iTregs 在控制从生命早期到成年期的哮喘中的相关性、Treg 功能的潜在机制，以及利用我们目前的概念充分发挥 Tregs 的潜力来限制疾病发展和进展的前景。
