Shevach Ethan M, Thornton Angela M
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, USA.
Immunol Rev. 2014 May;259(1):88-102. doi: 10.1111/imr.12160.
Foxp3(+) T-regulatory cells (Tregs) are primarily generated in the thymus (tTreg), but also may be generated extrathymically at peripheral sites (pTreg), or induced in cell culture (iTreg) in the presence of transforming growth factor β (TGFβ). A major unresolved issue is how these different populations of Tregs exert their suppressive function in vivo. We have developed novel systems in which the function of Tregs can be evaluated in vivo in normal mice. Our studies demonstrate that one prominent mechanism of action of polyclonal tTregs is to inhibit T-effector cell trafficking to the target organ, while antigen-specific iTregs primarily prevent T-cell priming by acting on antigen-presenting dendritic cells (DCs). Interleukin-10 (IL-10) plays an important role in the suppressive function of antigen-specific iTregs by controlling the expression of MARCH1 and CD83 on the DC. Activated tTregs may mediate infectious tolerance by delivery of cell surface-expressed TGFβ to naive responder T cells to generate pTregs. Manipulation of Treg function will require the ability to differentiate tTregs from pTregs and iTregs. The expression of the transcription factor Helios has proven to be a useful marker for the identification of stable tTregs in both mouse and human.
叉头框蛋白3（Foxp3）阳性调节性T细胞（Tregs）主要在胸腺中产生（胸腺来源的调节性T细胞，tTreg），但也可能在外周部位胸腺外产生（外周来源的调节性T细胞，pTreg），或在转化生长因子β（TGFβ）存在的情况下在细胞培养中诱导产生（诱导性调节性T细胞，iTreg）。一个主要未解决的问题是这些不同群体的Tregs如何在体内发挥其抑制功能。我们已经开发出了新的系统，在该系统中可以在正常小鼠体内评估Tregs的功能。我们的研究表明，多克隆tTregs的一个突出作用机制是抑制效应T细胞向靶器官的迁移，而抗原特异性iTregs主要通过作用于抗原呈递树突状细胞（DCs）来防止T细胞致敏。白细胞介素10（IL-10）通过控制DC上MARCH1和CD83的表达，在抗原特异性iTregs的抑制功能中发挥重要作用。活化的tTregs可能通过将细胞表面表达的TGFβ传递给幼稚应答T细胞以产生pTregs来介导感染性耐受。对Treg功能的操控将需要能够区分tTregs与pTregs和iTregs。转录因子Helios的表达已被证明是在小鼠和人类中鉴定稳定tTregs的有用标志物。
