Kinetics of T Helper Subsets and Associated Cytokines Correlate Well with the Clinical Activity of Graft-Versus-Host Disease
Kinetics of T Helper Subsets and Associated Cytokines Correlate Well with the Clinical Activity of Graft-Versus-Host Disease
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DOI：
10.1371/journal.pone.0044416
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发表时间：
2012-09-05
期刊：
影响因子：
3.7
通讯作者：
Chiu, Chang-Fang
中科院分区：
文献类型：
--
作者：
Yeh, Su-Peng;Liao, Yu-Min;Chiu, Chang-Fang
背景：CD4（+）干扰素(IFN)- γ (+) T细胞（Th1）和CD4（+）白细胞介素(IL)-4(+) T细胞（Th2）极化在移植物抗宿主病（GVHD）的发病机制中至关重要。然而，这一假设在很大程度上是基于Parent-into-F1 GVHD模型的动物实验。在现实世界中，Th1、Th2和相关细胞因子的动力学与GVHD的临床活性之间的因果关系尚不清楚。方法：连续27例患者接受同种异体外周血干细胞移植后，从第0天至第210天（无GVHD患者）或第300天（慢性GVHD患者），每周前瞻性采集外周血。流式细胞术检测CD4(+) T细胞内Th1和Th2的频率，ELISA检测血浆中ifn - γ、IL-12、IL-4和IL-10的频率。主要发现：Th1、Th2频率、血浆IL-10和ifn - γ的动力学通常与GVHD的活性相吻合，而不是预测。当急性或慢性GVHD发生时，这些标志物显著升高。在免疫抑制治疗的临床过程中，IL-10的动力学与GVHD的活性尤其相关。对于肝性GVHD患者，血浆IL-10水平与肝损伤严重程度呈正相关。在急性GVHD中，Th2的频率也明显更高，而在慢性GVHD中，Th2的频率往往更高。有趣的是，Th1和Th2的频率之间存在非常好的正相关（r = 0.951, p< 0.001）。血浆IL-4、IL-12水平与GVHD活性无相关性。结论：CD4(+) T细胞内Th1、Th2的频率以及血浆IL-10和ifn - γ是GVHD的良好生物标志物。血浆IL-10也可用于监测治疗反应性。此外，Th1和Th2可能都参与了GVHD的发病机制。
Background: CD4(+) interferon (IFN)-gamma(+) T cell (Th1) and CD4(+) interleukin (IL)-4(+) T cell (Th2) polarizations are crucial in the pathogenesis of graft-versus-host disease (GVHD). However, this hypothesis is largely based on animal experiments of Parent-into-F1 GVHD model. The causal relationship between kinetics of Th1, Th2 and associated cytokines and the clinical activity of GVHD in a real world situation remains unknown.Methodology: Peripheral blood was collected every week prospectively from Day 0 to Day 210 (patients without GVHD) or Day 300 (patients with chronic GVHD) after allogeneic peripheral blood stem cell transplantation in consecutive 27 patients. The frequencies of Th1 and Th2 within CD4(+) T cells were determined by flow cytometry and pplasma IFN-gamma, IL-12, IL-4, and IL-10 were determined by ELISA.Principal Findings: Kinetics of Th1, Th2 frequency, and the plasma IL-10 and IFN-gamma more commonly coincided with, rather than predicted, the activity of GVHD. These markers are significantly higher when acute or chronic GVHD developed. The kinetics of IL-10 is especially correlated well with the activity of GVHD during clinical course of immunosuppressive treatment. For patients with hepatic GVHD, there is a positive correlation between plasma IL-10 levels and the severity of hepatic injury. The frequency of Th2 is also significant higher in acute GVHD and tends to be higher in chronic GVHD. Interestingly, there is a very good positive correlation between the frequency of Th1 and Th2 (r = 0.951, p< 0.001). The plasma level of IL-4 and IL-12 are not associated with the activity of GVHD.Conclusions: The frequency of Th1, Th2 within CD4(+) T cells and plasma IL-10 and IFN-gamma are good biomarkers of GVHD. Plasma IL-10 can also be used to monitor the therapeutic responsiveness. Furthermore, both Th1 and Th2 likely contribute to the pathogenesis of GVHD.