Department of Pathology, University of Florida, Gainesville, Florida, United States of America.
PLoS One. 2009 Nov 24;4(11):e7980. doi: 10.1371/journal.pone.0007980.
CD25, a component of the IL-2 receptor, is important in T cell proliferation, activation induced cell death, as well as the actions of both regulatory (Treg) and effector (Teff) T cells. Recent genome wide association studies have implicated the CD25 locus as an important region for genetic susceptibility to a number of autoimmune disorders, with serum levels of soluble CD25 receptor (sCD25) serving as a potential phenotypic marker for this association. However, the functional impact of CD25 cleavage, as well as the influence of sCD25 on immunoregulatory activities, remain largely unknown and form the basis of this effort.
METHODOLOGY/PRINCIPAL FINDINGS: The generation of sCD25 by Treg (CD4(+)CD25(+)) and Teff (CD4(+)CD25(-)) cells was examined during in vitro suppression assays, efforts that demonstrated constitutive and stable surface CD25 expression on Treg throughout the period of in vitro assessment. In contrast, Teff cells increased CD25 expression during the process of in vitro suppression, with supernatant sCD25 levels correlating to the amount of cellular proliferation. Interestingly, under serum-free conditions, Tregs partially lost their characteristic anergic and suppressive properties. sCD25 supplementation at physiological concentrations to serum free in vitro suppression assays reduced Teff proliferation without specifically influencing suppression. Indeed, sCD25 production within these cultures correlated with cell death.
CONCLUSIONS/SIGNIFICANCE: These results support the notion that sCD25 functions as both a surrogate marker of T cell activation as well as an indicator of subsequent cellular death. In addition, the role of CD25 in immunomodulation is likely dependent on the local inflammatory milieu, with molecules capable of modulating surface CD25 expression playing a key role in defining immune responsiveness.
白细胞介素 2 受体的组成部分 CD25 对于 T 细胞增殖、激活诱导的细胞死亡以及调节性 (Treg) 和效应性 (Teff) T 细胞的作用都很重要。最近的全基因组关联研究表明，CD25 基因座是许多自身免疫性疾病遗传易感性的重要区域，可溶性 CD25 受体 (sCD25) 的血清水平可作为这种关联的潜在表型标志物。然而，CD25 切割的功能影响以及 sCD25 对免疫调节活性的影响在很大程度上仍然未知，这也是本研究的基础。
方法/主要发现：在体外抑制实验中研究了 Treg（CD4+CD25+）和 Teff（CD4+CD25-）细胞产生 sCD25 的情况，实验表明 Treg 在整个体外评估期间持续表达稳定的表面 CD25。相比之下，Teff 细胞在体外抑制过程中增加 CD25 表达，上清液 sCD25 水平与细胞增殖量相关。有趣的是，在无血清条件下，Treg 部分失去其特征性的无能和抑制特性。在无血清的体外抑制实验中，补充生理浓度的 sCD25 可减少 Teff 增殖，但不会特异性影响抑制作用。事实上，这些培养物中的 sCD25 产生与细胞死亡相关。
结论/意义：这些结果支持 sCD25 既可以作为 T 细胞活化的替代标志物，也可以作为随后细胞死亡的指标的观点。此外，CD25 在免疫调节中的作用可能取决于局部炎症环境，能够调节表面 CD25 表达的分子在定义免疫反应性方面起着关键作用。
