Maggi Enrico, Cosmi Lorenzo, Liotta Francesco, Romagnani Paola, Romagnani Sergio, Annunziato Francesco
Center of Research, Transfer, High Education MCIDNENT, University of Florence, Firenze, Italy.
Autoimmun Rev. 2005 Nov;4(8):579-86. doi: 10.1016/j.autrev.2005.04.010.
Several types of T regulatory (Treg) cells have been described in both mice and humans, including natural or professional (CD4+CD25+ T cells) and adaptive (Th3 and Tr1 cells) Treg cells. The former develops in the thymus and results in an endogeneous long-lived population of self-antigen-specific T cells in the periphery poised to prevent potentially autoimmune reactions. The second subset develops as a consequence of activation of mature T cells under particular conditions of sub-optimal antigen exposure and/or costimulation. Natural Treg cells are positively selected in the cortex through their TCR interactions with self-peptides presented by thymic stromal cells. It is likely that this high-affinity recognition results in signals rendering them anergic and able to produce anti-apoptoptic molecules which protect them from negative selection. Recently, small subsets of CD4+CD25+ and of CD8+CD25+ cells sharing similar characteristics have been detected in human fetal and post-natal thymuses. Both CD4+CD25+ and CD8+CD25+ human thymocytes express Foxp3 and GITR mRNA, as well as surface CCR8 and TNFR2 and cytoplasmic CTLA-4 proteins, which are common features of mature Treg cells. Following activation they do not proliferate or produce cytokines, but express surface CTLA-4 and TGF-beta1. They suppress the proliferation of autologous CD4+CD25- thymocytes to allogeneic stimulation by a contact-dependent mechanism related to the combined action of surface CTLA-4 and TGF-beta leading to the inhibition of the IL-2R alpha chain on target T cells. Lastly, both CD4+CD25+ and CD8+CD25+ Treg thymocytes exert strong suppressive activity on Th1, but much lower on Th2 cells, since these latter may escape from suppression via their ability to respond to growth factors other than IL-2. Treg cells that develop in, and emerge from, the thymus are certainly responsible for the maintenance of self-tolerance and prevention of autoimmune disorders. The result that Th1 cells are highly susceptible to the suppressive activity of Treg thymocytes is consistent with the important role of these cells in protecting against the Th1-mediated immune response to autoantigens.
在小鼠和人类中均已描述了几种类型的调节性T（Treg）细胞，包括天然或专职性（CD4 + CD25 + T细胞）和适应性（Th3和Tr1细胞）Treg细胞。前者在胸腺中发育，在外周形成内源性长寿的自身抗原特异性T细胞群体，随时准备预防潜在的自身免疫反应。第二亚群是成熟T细胞在次优抗原暴露和/或共刺激的特定条件下激活的结果。天然Treg细胞通过其TCR与胸腺基质细胞呈递的自身肽相互作用而在皮质中被阳性选择。这种高亲和力识别可能产生使它们无反应并能够产生抗凋亡分子的信号，从而保护它们免受阴性选择。最近，在人类胎儿和产后胸腺中检测到具有相似特征的CD4 + CD25 +和CD8 + CD25 +细胞的小亚群。人CD4 + CD25 +和CD8 + CD25 +胸腺细胞均表达Foxp3和GITR mRNA，以及表面CCR8和TNFR2以及细胞质CTLA-4蛋白，这些是成熟Treg细胞的共同特征。激活后，它们不增殖或产生细胞因子，但表达表面CTLA-4和TGF-β1。它们通过与表面CTLA-4和TGF-β的联合作用相关的接触依赖性机制抑制自体CD4 + CD25-胸腺细胞对同种异体刺激的增殖，从而导致靶T细胞上IL-2Rα链的抑制。最后，CD4 + CD25 +和CD8 + CD25 + Treg胸腺细胞对Th1均具有强大的抑制活性，但对Th2细胞的抑制活性则低得多，因为后者可能通过其对IL-2以外的生长因子作出反应的能力而逃避抑制。在胸腺中发育并从胸腺中出现的Treg细胞无疑负责维持自身耐受性和预防自身免疫性疾病。Th1细胞对Treg胸腺细胞的抑制活性高度敏感的结果与这些细胞在防止针对自身抗原的Th1介导的免疫反应中的重要作用是一致的。
