tTregs, pTregs, and iTregs: similarities and differences.

tTregs, pTregs, and iTregs: similarities and differences.
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DOI:
10.1111/imr.12160
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发表时间:
2014-05
影响因子:
8.7
通讯作者:
Thornton AM
Thornton AM
中科院分区:
医学1区
文献类型:
--
作者:
Shevach EM;Thornton AM

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Foxp3+T-调节性细胞(Treg)主要产生于胸腺(TTreg),也可在胸腺外的外周部位(PTreg)产生,也可在转化生长因子β(β)存在下在细胞培养(ITreg)中诱导。一个尚未解决的主要问题是,这些不同的Treg群体如何在体内发挥其抑制功能。我们已经开发了新的系统,其中Tregs的功能可以在正常小鼠体内进行评估。我们的研究表明,多克隆tTregs的一个重要作用机制是抑制T效应细胞向靶器官的转运,而抗原特异性iTregs主要通过作用于抗原提呈树突状细胞(DC)来阻止T细胞的启动。白介素10(IL-10)通过调控DC表面March1和CD83的表达,在抑制抗原特异性iTregs的功能中发挥重要作用。激活的tTregs可能通过将细胞表面表达的转化生长因子β传递到初始应答T细胞来产生pTregs,从而介导感染耐受。Treg函数的操作将需要区分tTregs与pTregs和iTregs的能力。转录因子Helios的表达已被证明是鉴定小鼠和人的稳定tTregs的有用标记。
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 man.
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