Stem Cell Research Lab, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
PLoS One. 2012;7(9):e44416. doi: 10.1371/journal.pone.0044416. Epub 2012 Sep 5.
CD4(+)interferon (IFN)-γ(+) 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.
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-γ, IL-12, IL-4, and IL-10 were determined by ELISA.
Kinetics of Th1, Th2 frequency, and the plasma IL-10 and IFN-γ 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.
The frequency of Th1, Th2 within CD4(+) T cells and plasma IL-10 and IFN-γ 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.
CD4(+)干扰素（IFN)-γ(+)T 细胞（Th1）和 CD4(+)白细胞介素（IL)-4(+)T 细胞（Th2）的极化在移植物抗宿主病（GVHD）的发病机制中至关重要。然而，这一假说在很大程度上是基于父母到 F1 的 GVHD 动物实验模型。在真实情况下，Th1、Th2 及其相关细胞因子的动力学与 GVHD 的临床活动之间的因果关系尚不清楚。
连续 27 例异基因外周血造血干细胞移植后，前瞻性每周采集外周血，从第 0 天至第 210 天（无 GVHD 患者）或第 300 天（慢性 GVHD 患者）。通过流式细胞术测定 CD4(+)T 细胞内 Th1 和 Th2 的频率，通过 ELISA 测定血浆 IFN-γ、IL-12、IL-4 和 IL-10。
Th1、Th2 频率以及血浆 IL-10 和 IFN-γ 的动力学通常与 GVHD 的活性相符，而不是预测。当急性或慢性 GVHD 发生时，这些标志物明显升高。在免疫抑制治疗过程中，IL-10 的动力学与 GVHD 的活性尤其相关。对于肝 GVHD 患者，血浆 IL-10 水平与肝损伤的严重程度呈正相关。急性 GVHD 患者 Th2 频率也显著升高，慢性 GVHD 患者 Th2 频率趋于升高。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）。IL-4 和 IL-12 血浆水平与 GVHD 活性无关。
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 还可用于监测治疗反应性。此外，Th1 和 Th2 可能都有助于 GVHD 的发病机制。
