Department of Dermatology, University Hospital Heidelberg, Heidelberg, Germany.
J Immunol. 2010 Apr 1;184(7):3408-16. doi: 10.4049/jimmunol.0901751. Epub 2010 Mar 5.
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) require activation to develop their full suppressive capacity. Similar to conventional T cells, Tregs can be activated via their TCRs; however, other means may be in place. We injected naive and nonactivated Tregs, being CD69(-)CD44(low)CD62L(+) into mice, and analyzed their phenotype after sensitization or challenge with the contact sensitizer 2,4,6-trinitro-1-chlorobenzene. We found that Tregs acquired an activated phenotype (CD69(+)CD44(high)CD62L(-)) in the draining lymph node after sensitization. In contrast, Ag challenge activated Tregs in the blood. This tissue-specific activation was induced by ATP, which was released at the respective tissue sites after sensitization or challenge, respectively. To demonstrate that activation was also essential for the induction of the suppressive function of Tregs, Tregs were treated with ATP receptor antagonists. In this study, we show that ATP receptor antagonists abrogated the suppressive effects of injected naive Tregs in contact hypersensitivity reactions. Thus, these data indicate that activation of Tregs via ATP in vivo provides a novel pathway of stimulating the suppressive function of Tregs.
CD4(+)CD25(+)Foxp3(+) 调节性 T 细胞（Tregs）需要激活才能发挥其完全抑制功能。与常规 T 细胞类似，Tregs 可以通过其 TCR 被激活；然而，可能还有其他方法。我们将幼稚和非激活的 Tregs（CD69(-)CD44(low)CD62L(+)）注入小鼠体内，并在用接触致敏剂 2,4,6-三硝基-1-氯苯敏化或挑战后分析其表型。我们发现 Tregs 在致敏后引流淋巴结中获得激活表型（CD69(+)CD44(high)CD62L(-)）。相比之下，Ag 挑战在血液中激活了 Tregs。这种组织特异性激活是由分别在致敏或挑战后释放的 ATP 诱导的。为了证明激活对于诱导 Tregs 的抑制功能也是必需的，我们用 ATP 受体拮抗剂处理 Tregs。在这项研究中，我们表明 ATP 受体拮抗剂阻断了注入的幼稚 Tregs 在接触超敏反应中的抑制作用。因此，这些数据表明，体内通过 ATP 激活 Tregs 为刺激 Tregs 的抑制功能提供了一种新途径。
