Center for Infectious Medicine (CIM), F59, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523.
Microbiol Spectr. 2016 Dec;4(6). doi: 10.1128/microbiolspec.TBTB2-0006-2016.
Immunity against Mycobacterium tuberculosis requires a balance between adaptive immune responses to constrain bacterial replication and the prevention of potentially damaging immune activation. Regulatory T (Treg) cells express the transcription factor Foxp3+ and constitute an essential counterbalance of inflammatory Th1 responses and are required to maintain immune homeostasis. The first reports describing the presence of Foxp3-expressing CD4+ Treg cells in tuberculosis (TB) emerged in 2006. Different Treg cell subsets, most likely specialized for different tissues and microenvironments, have been shown to expand in both human TB and animal models of TB. Recently, additional functional roles for Treg cells have been demonstrated during different stages and spectrums of TB disease. Foxp3+ regulatory cells can quickly expand during early infection and impede the onset of cellular immunity and persist during chronic TB infection. Increased frequencies of Treg cells have been associated with a detrimental outcome of active TB, and may be dependent on the M. tuberculosis strain, animal model, local environment, and the stage of infection. Some investigations also suggest that Treg cells are required together with effector T cell responses to obtain reduced pathology and sterilizing immunity. In this review, we will first provide an overview of the regulatory cells and mechanisms that control immune homeostasis. Then, we will review what is known about the phenotype and function of Treg cells from studies in human TB and experimental animal models of TB. We will discuss the potential role of Treg cells in the progression of TB disease and the relevance of this knowledge for future efforts to prevent, modulate, and treat TB.
针对结核分枝杆菌的免疫需要适应性免疫反应和防止潜在的免疫激活损伤之间的平衡。调节性 T（Treg）细胞表达转录因子 Foxp3+，构成炎症性 Th1 反应的必要制衡，是维持免疫稳态所必需的。2006 年首次报道了结核分枝杆菌（TB）中存在表达 Foxp3 的 CD4+Treg 细胞。已经表明，在人类 TB 和 TB 动物模型中，不同的 Treg 细胞亚群（最有可能专门针对不同的组织和微环境）会扩增。最近，在 TB 疾病的不同阶段和谱中，已经证明了 Treg 细胞具有额外的功能作用。Foxp3+调节性细胞可以在早期感染期间迅速扩增，阻碍细胞免疫的发生，并在慢性 TB 感染期间持续存在。Treg 细胞的频率增加与活动性 TB 的不良预后相关，并且可能依赖于结核分枝杆菌株、动物模型、局部环境和感染阶段。一些研究还表明，Treg 细胞与效应 T 细胞反应一起是获得减少的病理学和杀菌免疫所必需的。在这篇综述中，我们将首先概述控制免疫稳态的调节细胞和机制。然后，我们将回顾从人类 TB 和 TB 实验动物模型研究中了解到的 Treg 细胞的表型和功能。我们将讨论 Treg 细胞在 TB 疾病进展中的潜在作用，以及这些知识对未来预防、调节和治疗 TB 的相关性。
