Wang Jun, Ioan-Facsinay Andreea, van der Voort Ellen I H, Huizinga Tom W J, Toes René E M
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Immunol. 2007 Jan;37(1):129-38. doi: 10.1002/eji.200636435.
Foxp3 plays a key role in CD4+ CD25+ T(reg) cell function in mice and represents a specific marker for these cells. Despite the strong association between FOXP3 expression and regulatory function in fresh human T cells, little is known about the dynamics of endogenous FOXP3 expression and its relation to the suppressive function in activated human T cells. Here, we addressed the dynamics of FOXP3 expression during human CD4+ T cell activation by plate-bound anti-CD3 Ab as well as the relationship between its expression and regulatory function at the single-cell level. Our data show that FOXP3 is expressed in a high percentage of activated T cells after in vitro stimulation of human CD4+ CD25- cells. FOXP3 expression is strongly associated with hyporesponsiveness of activated T cells, but is not directly correlated with their suppressive capabilities, as we demonstrate that it is also expressed in activated nonsuppressive T cells. However, in this nonsuppressive T cell population, FOXP3 expression is transient, while it is stably expressed in activated T cells that do display suppressive function, and in natural CD4+ CD25++ T(reg) cells. These data indicate that expression of endogenous FOXP3, in humans, is not sufficient to induce regulatory T cell activity or to identify T(reg) cells.
Foxp3在小鼠CD4+ CD25+ T（调节性）细胞功能中起关键作用，是这些细胞的特异性标志物。尽管新鲜人T细胞中FOXP3表达与调节功能之间存在密切关联，但关于内源性FOXP3表达的动态变化及其与活化人T细胞抑制功能的关系却知之甚少。在此，我们探讨了人CD4+ T细胞被板结合抗CD3抗体激活过程中FOXP3表达的动态变化，以及在单细胞水平上其表达与调节功能之间的关系。我们的数据表明，体外刺激人CD4+ CD25-细胞后，高比例的活化T细胞表达FOXP3。FOXP3表达与活化T细胞的低反应性密切相关，但与它们的抑制能力无直接关联，因为我们证明它也在活化的非抑制性T细胞中表达。然而，在这个非抑制性T细胞群体中，FOXP3表达是短暂的，而在确实具有抑制功能的活化T细胞以及天然CD4+ CD25++ T（调节性）细胞中，它是稳定表达的。这些数据表明，在人类中，内源性FOXP3的表达不足以诱导调节性T细胞活性或识别T（调节性）细胞。
