Alberta Transplant Institute and Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
PLoS One. 2012;7(11):e43937. doi: 10.1371/journal.pone.0043937. Epub 2012 Oct 11.
CMV-specific T-cells are crucial to control CMV-replication post-transplant. Regulatory T-cells (T-regs) are associated with a tolerant immune state and may contribute to CMV-replication. However, T-cell subsets such as T-regs and IL-17 producing T-cells (Th-17) are not well studied in this context. We explored T-regs and Th-17 frequencies during CMV-replication after transplantation.
We prospectively evaluated 30 transplant patients with CMV-viremia. We quantified CMV-specific CD4(+) and CD8(+) T-cells, T-regs (CD4(+)CD25(+)FoxP3(+)) and Th-17 frequencies using flow-cytometry and followed patients requiring anti-viral treatment. Two subsets were compared: anti-viral treatment requirement (n = 20) vs. spontaneous clearance of viremia (n = 10).
Higher initial CMV-specific CD4(+) T-cells and lower T-regs were observed in patients with spontaneous clearance (p = 0.043; p = 0.021 respectively). Using a ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of viral clearance with 80% sensitivity and 90% specificity (p = 0.001). One month after stop of treatment, the same correlation was observed in patients protected from CMV-relapse. The ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of relapse with 85% sensitivity and 86% specificity (p = 0.004). Th-17 responses were not correlated with virologic outcomes.
This study provides novel insights into T-regs and Th-17 subpopulations during CMV-replication after transplantation. These preliminary data suggest that measurement of CMV-specific CD4(+) T-cells together with T-regs has value in predicting spontaneous clearance of viremia and relapse.
CMV 特异性 T 细胞对于移植后控制 CMV 复制至关重要。调节性 T 细胞（T-regs）与耐受的免疫状态相关，并可能有助于 CMV 复制。然而，在这种情况下，T-regs 和产生白细胞介素 17 的 T 细胞（Th-17）等 T 细胞亚群尚未得到充分研究。我们在移植后 CMV 复制期间探索了 T-regs 和 Th-17 的频率。
我们前瞻性评估了 30 例 CMV 病毒血症移植患者。我们使用流式细胞术定量评估 CMV 特异性 CD4(+)和 CD8(+)T 细胞、T-regs（CD4(+)CD25(+)FoxP3(+)）和 Th-17 的频率，并随访需要抗病毒治疗的患者。比较了两个亚组：抗病毒治疗需求（n=20）与病毒血症自发清除（n=10）。
自发清除病毒血症的患者初始 CMV 特异性 CD4(+)T 细胞更高，T-regs 更低（p=0.043；p=0.021）。使用 CMV 特异性 CD4(+)T 细胞与 T-regs 的比值可以预测病毒清除，具有 80%的敏感性和 90%的特异性（p=0.001）。在停止治疗一个月后，在免受 CMV 复发的患者中观察到相同的相关性。CMV 特异性 CD4(+)T 细胞与 T-regs 的比值可以预测复发，具有 85%的敏感性和 86%的特异性（p=0.004）。Th-17 反应与病毒学结果无关。
这项研究为移植后 CMV 复制期间 T-regs 和 Th-17 亚群提供了新的见解。这些初步数据表明，测量 CMV 特异性 CD4(+)T 细胞与 T-regs 一起具有预测病毒血症自发清除和复发的价值。
