University of Colorado Denver School of Medicine, Aurora, CO, USA.
Virology. 2010 Mar 15;398(2):158-67. doi: 10.1016/j.virol.2009.11.038. Epub 2009 Dec 24.
CMV infection is characterized by high of frequencies of CD27-CD28- T cells. Here we demonstrate that CMV-specific CD4+CD27-CD28- cells are regulatory T cells (TR). CD4+CD27-CD28- cells sorted from CMV-stimulated PBMC of CMV-seropositive donors inhibited de novo CMV-specific proliferation of autologous PBMC in a dose-dependent fashion. Compared with the entire CMV-stimulated CD4+ T-cell population, higher proportions of CD4+CD27-CD28- TR expressed FoxP3, TGFbeta, granzyme B, perforin, GITR and PD-1, lower proportions expressed CD127 and PD1-L and similar proportions expressed CD25, CTLA4, Fas-L and GITR-L. CMV-CD4+CD27-CD28- TR expanded in response to IL-2, but not to CMV antigenic restimulation. The anti-proliferative effect of CMV-CD4+CD27-CD28- TR significantly decreased after granzyme B or TGFbeta inhibition. The CMV-CD4+CD27-CD28- TR of HIV-infected and uninfected donors had similar phenotypes and anti-proliferative potency, but HIV-infected individuals had higher proportions of CMV-CD4+CD27-CD28- TR. The CMV-CD4+CD27-CD28- TR may contribute to the downregulation of CMV-specific and nonspecific immune responses of CMV-infected individuals.
巨细胞病毒（CMV）感染的特征是 CD27-CD28- T 细胞的高频率。在这里，我们证明 CMV 特异性 CD4+CD27-CD28-细胞是调节性 T 细胞（TR）。从 CMV 阳性供体的 CMV 刺激的 PBMC 中分选的 CD4+CD27-CD28-细胞以剂量依赖性方式抑制自身 PBMC 的 CMV 特异性增殖的从头发生。与整个 CMV 刺激的 CD4+T 细胞群体相比，CD4+CD27-CD28-TR 表达更多的 FoxP3、TGFbeta、颗粒酶 B、穿孔素、GITR 和 PD-1，表达更少的 CD127 和 PD1-L，表达相似比例的 CD25、CTLA4、Fas-L 和 GITR-L。CMV-CD4+CD27-CD28-TR 响应 IL-2 而不是 CMV 抗原再刺激而扩增。CMV-CD4+CD27-CD28-TR 的抗增殖作用在颗粒酶 B 或 TGFbeta 抑制后显著降低。HIV 感染和未感染供体的 CMV-CD4+CD27-CD28-TR 具有相似的表型和抗增殖效力，但 HIV 感染个体的 CMV-CD4+CD27-CD28-TR 比例更高。CMV-CD4+CD27-CD28-TR 可能有助于下调 CMV 感染个体的 CMV 特异性和非特异性免疫反应。
