Basso Alexandre S, Cheroutre Hilde, Mucida Daniel
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo - UNIFESP, São Paulo, SP, Brazil.
Cell Res. 2009 Apr;19(4):399-411. doi: 10.1038/cr.2009.26.
For more than two decades, immunologists have been using the so-called Th1/Th2 paradigm to explain most of the phenomena related to adaptive immunity. The Th1/Th2 paradigm implied the existence of two different, mutually regulated, CD4(+) T helper subsets: Th1 cells, driving cell-mediated immune responses involved in tissue damage and fighting infection against intracellular parasites; and Th2 cells that mediate IgE production and are particularly involved in eosinophilic inflammation, allergy and clearance of helminthic infections. A third member of the T helper set, IL-17-producing CD4(+) T cells, now called Th17 cells, was recently described as a distinct lineage that does not share developmental pathways with either Th1 or Th2 cells. The Th17 subset has been linked to autoimmune disorders, being able to produce IL-17, IL-17F and IL-21 among other inflammatory cytokines. Interestingly, it has been reported that there is not only a cross-regulation among Th1, Th2 and Th17 effector cells but there is also a dichotomy in the generation of Th17 and T regulatory cells. Therefore, Treg and Th17 effector cells arise in a mutually exclusive fashion, depending on whether they are activated in the presence of TGF-beta or TGF-beta plus inflammatory cytokines such as IL-6. This review will address the discovery of the Th17 cells, and recent progress on their development and regulation.
二十多年来,免疫学家一直使用所谓的Th1/Th2范式来解释大多数与适应性免疫相关的现象。Th1/Th2范式意味着存在两种不同的、相互调节的CD4(+)辅助性T细胞亚群:Th1细胞,驱动参与组织损伤的细胞介导免疫反应并对抗细胞内寄生虫感染;以及Th2细胞,介导IgE产生,尤其参与嗜酸性粒细胞炎症、过敏和清除蠕虫感染。辅助性T细胞群体的第三个成员,即产生IL-17的CD4(+) T细胞,现在称为Th17细胞,最近被描述为一个独特的谱系,它与Th1或Th2细胞没有共同的发育途径。Th17亚群与自身免疫性疾病有关,能够产生IL-17、IL-17F和IL-21等多种炎性细胞因子。有趣的是,据报道,Th1、Th2和Th17效应细胞之间不仅存在交叉调节,而且Th17细胞和调节性T细胞的产生也存在二分法。因此,调节性T细胞和Th17效应细胞以相互排斥的方式产生,这取决于它们是在TGF-β存在的情况下被激活,还是在TGF-β加上炎性细胞因子如IL-6的情况下被激活。本综述将阐述Th17细胞的发现及其在发育和调节方面的最新进展。