Transient regulatory T-cells: A state attained by all activated human T-cells
Transient regulatory T-cells: A state attained by all activated human T-cells
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DOI：
10.1016/j.clim.2006.10.014
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发表时间：
2007-04-01
影响因子：
8.6
通讯作者：
Karandikar, Nitin J.
中科院分区：
文献类型：
--
作者：
Pillai, Vinodh;Ortega, Sterling B.;Karandikar, Nitin J.
CD 4（+）CD 25（+）FOXP 3（+）调节性T细胞（T-CTL）是免疫系统的重要组成部分，负责抑制不良免疫反应。T细胞可以是胸腺来源的或外周诱导的，甚至来自CD 4（+）CD 25（-）FOXP 3（-）T细胞。FOXP 3表达和体外抑制活性被认为是这种专用且稳定的调节细胞谱系的独特标志。在这里，我们发现几乎所有的人CD 4（+）CD 25（-）FOXP 3（-）T细胞和CD 8（+）CD 25（-）FOXP 3（-）T细胞在活化过程中达到短暂的FOXP 3（+）CD 25（+）状态。在这种激活状态下，这些细胞具有典型的T细胞表型，因为它们表达相似的标记物并抑制自体CD 4（+）CD 25（-）T细胞的体外增殖。这种状态的特征在于抑制IFN-γ产生和稳健的TNF-α和IL-10产生。有趣的是，大多数活化细胞最终下调FOXP 3表达，伴随着抑制能力的下降。我们的研究结果表明，在人类中，FOXP 3表达和T-reg功能并不是T细胞稳定或独特谱系的唯一特征，但也可能是几乎所有T细胞都能达到的短暂状态。这些结果在解释使用FOXP 3和抑制活性作为读数的人类研究时需要谨慎，并表明除非证实稳定性，否则诱导“T细胞活化”的尝试可能矛盾地导致效应T细胞的诱导。(c)2006年爱思唯尔公司All rights reserved.
CD4(+)CD25(+)FOXP3(+) regulatory T-cells (T-regs) form an important arm of the immune system responsible for suppressing untoward immune responses. T-regs can be thymically derived or peripherally induced, even from CD4(+)CD25(-)FOXP3(-) T-cells. FOXP3 expression and in vitro suppressive activity are considered unique hallmarks of this dedicated and stable lineage of regulatory cells. Here we show that virtually all human CD4(+)CD25(-)FOXP3(-) T-cells and CD8(+)CD25(-)FOXP3(-) T-cells attain a transient FOXP3(+)CD25(+) state during activation. In this state of activation, these cells possess the classic phenotype of T-regs, in that they express similar markers and inhibit in vitro proliferation of autologous CD4(+)CD25(-) T-cells. This state is characterized by suppressed IFN-gamma production and robust TNF-alpha and IL-10 production. Interestingly, the great majority of the activated cells eventually downregulate FOXP3 expression, with a concomitant drop in suppressive ability. Our results show that, in humans, FOXP3 expression and T-reg functionality are not exclusive features of a stable or unique lineage of T-cells but may also be a transient state attained by almost all T-cells. These results warrant caution in interpreting human studies using FOXP3 and suppressive activity as readouts and suggest that attempts to induce "T-regs" may paradoxically result in induction of effector T-cells, unless stability is confirmed. (c) 2006 Elsevier Inc. All rights reserved.