Regulatory T cells
Regulatory T cells
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DOI：
10.1007/s00281-006-0043-2
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发表时间：
2006-08
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影响因子：
--
通讯作者：
S. Sakaguchi
中科院分区：
文献类型：
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作者：
S. Sakaguchi
我们的免疫系统保护我们免受免疫学家之间无数的巨大争议，并一直是潜在的病原微生物，同时避免了多年来几乎没有可信度，主要是因为与我们身体的成分一起作用;即，我们容忍缺乏可靠的标记来定义细胞，“自我”。免疫自身耐受的失败往往在抑制pheads的分子基础上的模糊性导致自身免疫性疾病的发展，这是罕见的，甚至一些supi的难以捉摸的性质估计折磨高达5%的人口。压抑的现象本身。然而，如果一个人虽然自身免疫性疾病的病因学是目前问自我耐受的机制应该，当在很大程度上是未知的，它是有据可查的，T细胞是它出错，直接导致自身免疫性疾病或许多自身免疫性疾病的关键介质，这样的一个，当加强，可以防止自身免疫性胰岛素依赖性糖尿病（IDDM），自身免疫性疾病，免疫性甲状腺炎和自身免疫性胃炎的实验证据越来越多，这表明某些恶性贫血的清除或灭活。此外，越来越多的调节性T细胞群可以打破正常健康个体具有潜力的天然自我耐受证据，导致各种致病性自我反应性T细胞的自发发育。例如，自身免疫性疾病。对移植耐受性免疫正常动物的研究也证实，自身抗原阳性的T细胞主动抑制，佐剂可诱导休眠的自身反应性T细胞转变为效应性T细胞，使其从排斥移植物中攻击一定的耐受性抗原，引发炎性组织损伤。状态此外，最近在细胞因子重自身反应性T细胞克隆方面的进展也很容易分离，研究表明，正常健康人外周血中分泌免疫抑制性细胞因子的T细胞具有调节性T细胞的作用，并通过自身分子的反复体外刺激而发挥作用。而且，许多肿瘤相关抗原识别移植物。这篇综述将讨论最近的进展，通过自体T细胞在癌症患者中，现在已经把我们的理解的关键作用的调节性T细胞是正常的自我成分，而不是异常prodin免疫耐受。突变基因的表达，表明肿瘤免疫的自身耐受性是由CD 4+维持的，部分是一种自身免疫。因此，当前免疫学中的关键问题之一是阐明调节性T细胞的存在与自身免疫危险性（或有时是有益）自身反应性T细胞抑制活性已经在各种动物中被提出是在生理或疾病状态下产生的，以及自20世纪80年代早期以来自身免疫性疾病的模型，它们是如何被调节以避免自身免疫性疾病的（Itoh等人，1999年）。例如，在（或不攻击自体肿瘤细胞）。一个更好的NOD（非肥胖糖尿病）小鼠或BB（生物育种）站在免疫大鼠的机制，自发发展的胰岛素依赖型糖尿病和自身不耐受性，将导致更好的治疗自身免疫性甲状腺炎，接种CD 4 T细胞的疾病，癌症和移植排斥。组织相容性正常动物有效地防止了在胸腺中T细胞成熟期间的未成熟TIDDM。另一方面，效应T细胞的表征表达了介导这些器官特异性自身免疫反应的多种多样的T细胞。
Our immune system protects us from a myriad of potengreat controversy among immunologists and has been tially pathogenic microorganisms while avoiding regiven little credibility for many years, largely because of acting with constituents of our body; ie, we are tolerant the paucity of reliable markers for defining the cell, the of “self.” Failure of immunologic self-tolerance often ambiguity in the molecular basis of suppressive pheleads to the development of autoimmune disease, which nomena, and even the elusive nature of some supis estimated to afflict up to 5% of the population. Alpressive phenomena themselves. Nevertheless, if one though the etiology of autoimmune disease is at present asks which mechanism of self-tolerance should, when largely unknown, it is well documented that T cells are it goes awry, directly lead to autoimmune disease or the key mediators of many autoimmune diseases, such which one, when strengthened, can prevent autoimas insulin-dependent diabetes mellitus (IDDM), autoimmune disease, accumulating experimental evidence mune thyroiditis, and autoimmune gastritis accompanow suggests that removal or inactivation of a certain nying pernicious anemia. Furthermore, there is mounting regulatory T cell population can break natural self-tolerevidence that normal healthy individuals harbor potenance, leading to spontaneous development of various tially pathogenic self-reactive T cells. For example, imautoimmune diseases. Studies on transplantation tolermunization of normal animals with a self-antigen in poance have also documented that T cells actively inhibit tent adjuvant can induce dormant self-reactive T cells to effector T cells from rejecting grafts in a certain tolerant attack the antigen, eliciting inflammatory tissue damage. state. Furthermore, recent advances in cytokine re-Self-reactive T cell clones can also easily be isolated search have revealed that T cells secreting immunosupfrom the peripheral blood of normal healthy individuals pressive cytokines behave as regulatory T cells and inby repeated in vitro stimulation with self-molecules. deed downregulate autoimmunity and responses to Moreover, many tumor-associated antigens recognized transplants. This review will discuss recent advances in by autologous T cells in cancer patients have now turned our understanding of the key role of regulatory T cells out to be normal self-constituents, not abnormal prodin immunologic tolerance. ucts of mutated genes, indicating that tumor immunity Self-Tolerance Is Maintained by CD4+ is in part an autoimmunity. One of the current key issues Regulatory T Cells in immunology is therefore to elucidate how potentially The existence of regulatory T cells with autoimmunehazardous (or sometimes beneficial) self-reactive T cells inhibitory activity has been suggested in various animal are generated in physiological or disease states, and models of autoimmune disease since the early 1980s how they are regulated to avoid autoimmune disease(references cited in Itoh et al., 1999). For example, in (or not to attack autologous tumor cells). A better under- NOD (non-obese diabetic) mice or BB (Bio-Breeding) standing of the mechanisms underlying immunologic rats, which spontaneously develop IDDM and autoimtolerance will lead to better treatments for autoimmune mune thyroiditis, inoculation with CD4 T cells from disease, cancer, and transplant rejection. histocompatible normal animals effectively prevented During T cell maturation in the thymus, immature T IDDM. On the other hand, characterization of effector T cells express an enormously diverse range of T cell cells mediating these organ-specific autoimmune …