T 细胞中穿孔素表达水平高：成人异基因干细胞移植后疱疹病毒再激活严重程度的早期预后标志物。

High level of perforin expression in T cells: An early prognostic marker of the severity of herpesvirus reactivation after allogeneic stem cell transplantation in adults.

机构信息

Department of Immunology, University Medical Center Utrecht, the Netherlands.

出版信息

Clin Infect Dis. 2010 Mar 1;50(5):717-25. doi: 10.1086/650455.

DOI:10.1086/650455

PMID:20121571

Abstract

BACKGROUND

Epstein-Barr virus (EBV) and cytomegalovirus reactivations are frequent complications of hematopoeitic allogeneic stem cell transplantation (SCT) because of a lack of T cell control after immunosuppression. Early diagnosis of reactivation and subsequent preemptive therapy relies on frequent viral load measurement. Additional virus-specific T cell reconstitution data could improve the predictive value of viral load detection for viral complications after transplantation. Here, we studied perforin expression in CD8(+) T cells as a measure of cytotoxic T cell capacity in relation to the occurrence of viral reactivation.

METHODS

In a prospective study, we monitored 40 patients during the first 3 months after transplantation and measured viral loads in combination with intracellular perforin expression in CD8(+) T cells.

RESULTS

Median perforin expression in CD8(+) T cells throughout follow-up was higher in patients with viral reactivations than in patients without viral reactivations (4.9% vs 2.3%; P = .001). The median percentage of perforin-expressing CD8(+) T cells in patients with high viral reactivations exceeding 1000 copies/mL (10.7%) was statistically significantly higher than that in patients with minor reactivations of 50-1000 copies (4.0%), that in patients with detectable EBV loads that did not exceed the detection limit of 50 copies/mL (2.9%), and that in patients without reactivations (0.8%). Patients with high viral reactivations reached a high percentage of perforin-expressing CD8(+) T cells (>10.2%) more often and faster than did patients with low viral loads (1000 copies/mL) or without viral reactivations. High perforin expression preceded high viral loads.

CONCLUSION

Perforin-expressing CD8(+) T cells may be useful as an easy-to-measure prognostic marker for identifying patients at risk for severe viral reactivation very soon after SCT.

摘要

背景

由于免疫抑制后缺乏 T 细胞控制，EBV 和巨细胞病毒再激活是异基因造血干细胞移植（SCT）后的常见并发症。早期诊断再激活和随后的抢先治疗依赖于频繁的病毒载量测量。额外的病毒特异性 T 细胞重建数据可以提高病毒载量检测对移植后病毒并发症的预测价值。在这里，我们研究了 CD8+T 细胞中穿孔素的表达，作为细胞毒性 T 细胞能力的指标，与病毒再激活的发生有关。

方法

在一项前瞻性研究中，我们在移植后 3 个月内监测了 40 例患者，并结合 CD8+T 细胞中的细胞内穿孔素表达测量了病毒载量。

结果

整个随访期间，病毒再激活患者的 CD8+T 细胞中穿孔素表达的中位数高于无病毒再激活患者（4.9%比 2.3%；P=.001）。高病毒再激活（超过 1000 拷贝/ml）患者中表达穿孔素的 CD8+T 细胞的中位数百分比（10.7%）明显高于病毒再激活较少（50-1000 拷贝）的患者（4.0%）、可检测到 EBV 载量但不超过 50 拷贝/ml 检测限的患者（2.9%）和无再激活的患者（0.8%）。高病毒再激活患者达到高表达穿孔素的 CD8+T 细胞（>10.2%）的百分比更高，速度更快，而病毒载量低（1000 拷贝/ml）或无病毒再激活的患者则更低。高穿孔素表达先于高病毒载量。