Foxp3+ Regulatory T Cells in Tuberculosis
Foxp3+ Regulatory T Cells in Tuberculosis
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DOI：
10.1007/978-1-4614-6111-1_9
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发表时间：
2013-01-01
期刊：
影响因子：
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通讯作者：
Urdahl, Kevin B.
中科院分区：
文献类型：
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作者：
Larson, Ryan P.;Shafiani, Shahin;Urdahl, Kevin B.
对结核分枝杆菌 (Mtb) 的免疫反应必须受到严格调节，以产生足够的反应来限制细菌的生长和传播，同时避免可能损害宿主组织的过度炎症。多种细胞类型、细胞表面分子和细胞因子都可能参与这种调节，但最近的研究表明，表达转录因子 Foxp3 的 CD4 T 细胞亚群（称为调节性 T (reg) 细胞）发挥着关键作用 [1-3]。尽管 T reg 细胞在结核病 (TB) 中的首次报道最近才出现（即 2006 年）[4, 5]，但我们已经对它们在结核病期间的活动有了很多了解。虽然 T reg 细胞可能确实通过预防结核病期间炎症介导的宿主组织损伤发挥了一些有益的作用，但迄今为止，其功能的这方面尚未得到充分研究。然而，显而易见的是，在 T 细胞对 Mtb 感染的最初反应期间，Mtb 会诱导 T reg 细胞的扩增，从而延迟适应性免疫的发生，这表明 Mtb 劫持了 T reg 细胞介导的免疫抑制，使其在肺部有增无减地复制，直到 T 细胞最终到达 [6]。在本章中，我们将首先概述 T 细胞对 Mtb 的延迟反应，并简要介绍调节性 T 细胞。然后，我们将回顾从对人群的观察中对 T reg 细胞的了解，讨论小鼠模型中揭示的机制见解，并推测这种理解与未来预防和治疗结核病的努力的相关性。
The immune response to Mycobacterium tuberculosis (Mtb) must be tightly regulated to mount a sufficient response to limit bacterial growth and dissemination while avoiding excessive inflammation that could damage host tissues. A wide variety of cell types, cell surface molecules, and cytokines are likely to contribute to this regulation, but recent studies have revealed that a subset of CD4 T cells expressing the transcription factor Foxp3, called regulatory T (reg) cells, play a critical role [1-3]. Although the first reports of T reg cells in tuberculosis (TB) occurred only recently (i.e., 2006) [4, 5], we have already gained many insights into their activity during TB. While it is likely that T reg cells do play some beneficial roles by preventing inflammation-mediated damage to host tissues during TB, this aspect of their function has not been well studied to date. What is clear, however, is that during the initial T cell response to Mtb infection, Mtb induces the expansions of T reg cells that delay the onset of adaptive immunity, suggesting that Mtb has hijacked T reg cell-mediated immune suppression to allow it to replicate unabated in the lung until T cells finally arrive [6]. In this chapter, we will first provide an overview of the delayed T cell response to Mtb and a brief introduction to regulatory T cells. We will then review what is known about T reg cells from observations in human populations, discuss mechanistic insights revealed in the mouse model, and speculate about the relevance of this understanding for future efforts to prevent and treat TB.