Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Immunol Invest. 2013;42(1):18-35. doi: 10.3109/08820139.2012.719563. Epub 2012 Oct 19.
In experimental and clinical settings Tregs prevent graft-versus-host disease (GvHD) by inhibiting the proliferation and function of conventional T cells (Tconv). The suppressive potency of Tregs might also lead to the inhibition of protective antiviral T cell responses. As the control of CMV reactivation is important to improve the clinical outcome in allogeneic HSCT, we analyzed the Treg reconstitution in CMV reactivating patients with and without GvHD (n=47) in the first 6 months following transplantation. Most importantly, CMV reactivation does not correlate with the numerical reconstitution of CD4(+)CD25(high)CD127(-) Tregs. During CMV reactivation the proportion of Tregs within the CD4(+) T cell population decreased significantly independent of GvHD manifestation. A comprehensive FACS analysis was performed in order to characterize the phenotype of Tregs and Tconv cells in greater detail for activation, co-stimulation, proliferation, suppressive function and migratory capability. Interestingly, Tregs of patients with CMV reactivation showed a significantly higher CXCR3 expression. CD4(+) Tconv cells expressed significantly higher protein levels of the proliferation marker Ki67 correlating with a numerical increase of CD4(+) T cells. Our results indicate that Tregs are not inhibiting pathogen clearance by Tconv following HSCT, which is of high relevance for future Treg cell-based clinical trials in allogeneic HSCT.
在实验和临床环境中，Treg 通过抑制常规 T 细胞（Tconv）的增殖和功能来预防移植物抗宿主病（GvHD）。Treg 的抑制作用也可能导致保护性抗病毒 T 细胞反应受到抑制。由于控制 CMV 再激活对于改善异基因 HSCT 的临床结果非常重要，我们分析了移植后前 6 个月内发生 CMV 再激活且有或无 GvHD 的患者（n=47）中的 Treg 重建情况。最重要的是，CMV 再激活与 CD4(+)CD25(high)CD127(-) Treg 的数量重建无关。在 CMV 再激活期间，Treg 在 CD4(+) T 细胞群中的比例显著下降，与 GvHD 表现无关。为了更详细地描述 Treg 和 Tconv 细胞的表型，我们进行了全面的 FACS 分析，以评估其激活、共刺激、增殖、抑制功能和迁移能力。有趣的是，CMV 再激活患者的 Treg 表现出明显更高的 CXCR3 表达。CD4(+) Tconv 细胞表达的增殖标志物 Ki67 蛋白水平明显更高，与 CD4(+) T 细胞数量的增加相关。我们的结果表明，Treg 不会在 HSCT 后抑制 Tconv 清除病原体，这对于未来异基因 HSCT 中的基于 Treg 细胞的临床试验具有重要意义。
