Regulatory T cells - a brief history and perspective
Regulatory T cells - a brief history and perspective
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DOI：
10.1002/eji.200737593
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发表时间：
2007-11-01
影响因子：
5.4
通讯作者：
Miyara, Makoto
中科院分区：
文献类型：
--
作者：
Sakaguchi, Shimon;Wing, Kajsa;Miyara, Makoto
现在广泛接受的是，正常的免疫系统具有专门用于免疫抑制的调节性T细胞群。最初发现，正常动物中的一些CD4（+）T细胞能够抑制自身免疫。对这种自身免疫抑制性CD4（+）T细胞群体的表征表明，它们组成性表达CD25分子，这使得有可能将它们与其他T细胞区分开来，描绘它们的发育途径，特别是它们的胸腺发育，并表征它们在体内和体外的有效免疫抑制活性。该标记还有助于鉴定具有相似功能和表型特征的人类调节性T细胞。最近的研究表明，CD25（+）CD4（+）调节性T细胞特异性表达转录因子Foxp3。Foxp3基因异常通过影响CD25+CD4+调节性T细胞的发育和功能，导致啮齿类动物和人类自身免疫性和炎症性疾病。这些在细胞和分子水平上的发现为Foxp3（+）CD25（+）CD4（+）调节性T细胞作为正常免疫系统不可或缺的细胞成分以及它们在建立和维持免疫自身耐受和免疫稳态中的关键作用提供了有力的证据。它们可用于临床治疗免疫性疾病和控制生理和病理免疫应答。
It is now widely accepted that the normal immune system harbors a regulatory T-cell population specialized for immune suppression. It was found initially that some CD4(+) T cells in normal animals were capable of suppressing autoimmunity. Characterization of this autoinimune-suppressive CD4(+) T cell population revealed that they constitutively expressed the CD25 molecule, which made it possible to distinguish them from other T cells, delineate their developmental pathways, in particular their thymic development, and characterize their potent in vivo and in vitro immunosuppressive activity. The marker also helped to identify human regulatory T cells with similar functional and phenotypic characteristics. Recent studies have shown that CD25(+)CD4(+) regulatory T cells specifically express the transcription factor Foxp3. Genetic anomaly of Foxp3 causes autoimmune and inflammatory disease in rodents and humans through affecting the development and function of CD25+CD4+ regulatory T cells. These findings at the cellular and molecular levels altogether provide firm evidence for Foxp3(+)CD25(+)CD4(+) regulatory T cells as an indispensable cellular constituent of the normal immune system and for their crucial roles in establishing and maintaining immunologic self-tolerance and immune homeostasis. They can be exploited for clinical use to treat immunological diseases and control physiological and pathological immune responses.