Expanding and converting regulatory T cells: a horizon for immunotherapy
Expanding and converting regulatory T cells: a horizon for immunotherapy
复制标题
DOI：
10.1007/s00005-009-0021-1
复制
发表时间：
2009-05-01
影响因子：
3.2
通讯作者：
Stepkowski, Stanislaw M.
中科院分区：
文献类型：
--
作者：
Khattar, Mithun;Chen, Wenhao;Stepkowski, Stanislaw M.
人类免疫系统是无数不同的细胞群体，每一个都有助于维持针对感染因子的有效和最佳免疫应答。在免疫系统中保持“自我检查”是很重要的，这样反应就不会失控，导致自身免疫性疾病的发展。调节性/抑制性T（Treg）细胞是抑制其他T细胞的活化、扩增和功能的特化T细胞亚群，从而通过对外来抗原和自身抗原的反应性之间的精细平衡来维持稳态。T细胞的特征在于白细胞介素（IL）-2受体α链（CD 25）的表面表达和叉头盒蛋白P3（FoxP 3）的细胞内表达。存在至少两种重要的Treg细胞功能群，即天然Treg（nTreg）和诱导Treg（iTreg），所述天然Treg（nTreg）连续来源于胸腺，所述诱导Treg（iTreg）由初始T细胞转化。nTreg和iTreg细胞两者的发育和功能均受若干因素调节，例如抗原T细胞受体、共刺激受体（即，细胞毒性T淋巴细胞相关抗原或CTLA-4）和细胞因子（IL-2、IL-10和肿瘤生长因子-β或TGF-β）。此外，TGF-β抑制剂ALK 5、维甲酸和雷帕霉素影响nTreg细胞的扩增和iTreg细胞在体外和体内的转化。Treg扩增的提高可用于治疗自身免疫性疾病和诱导移植耐受的治疗方法。
The human immune system is a myriad of diverse cellular populations, each contributing to maintaining an effective and optimal immune response against infectious agents. It is important to maintain a "self-check" in the immune system so that responses do not go haywire, leading to the development of autoimmune diseases. Regulatory/suppressor T (Treg) cells are a specialized subpopulation of T cells that suppress the activation, expansion, and function of other T cells, thereby maintaining homeostasis through a fine balance between reactivity to foreign and self antigens. Tregs are characterized by surface expression of interleukin (IL)-2 receptor alpha chain (CD25) and intracellular expression of forkhead box protein P3 (FoxP3). There are at least two important functional populations of Treg cells, namely natural Treg (nTreg), which are continuously derived from the thymus, and induced Treg (iTreg), which are converted from naive T cells. The development and function of both nTreg and iTreg cells are regulated by several factors, such as antigen T-cell receptor, co-stimulatory receptors (i.e., cytotoxic T lymphocyte-associated antigen, or CTLA-4), and cytokines (IL-2, IL-10, and tumor growth factor-beta, or TGF-beta). In addition, the TGF-beta inhibitor ALK5, retinoid acid, and rapamycin influence the expansion of nTreg cells and the conversion of iTreg cells in vitro and in vivo. The heightening of Treg expansion may be harnessed to therapeutic methods for the treatment of autoimmune diseases and the induction of transplantation tolerance.