Arimoto Kazue, Kadowaki Norimitsu, Ishikawa Takayuki, Ichinohe Tatsuo, Uchiyama Takashi
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Int J Hematol. 2007 Feb;85(2):154-62. doi: 10.1532/IJH97.06160.
CD4+CD25+ regulatory T-cells (Treg cells) that express Foxp3 protein play an important role in inducing and maintaining allogeneic tolerance and can inhibit graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT) in murine models. Thus, it is important to clarify the kinetics of Treg cell recovery and its correlation with the occurrence of GVHD in humans; however, whether there is a correlation between the frequency of Treg cells in peripheral blood and the occurrence of GVHD is controversial. We examined the recovery of Treg cells in peripheral blood after allogeneic SCT by quantitating FOXP3 messenger RNA (mRNA). Full donor chimerism was achieved within 1 month after SCT in all but 1 case. The ratios of the measured expression levels of FOXP3 mRNA to those of endogenous control genes rapidly recovered to the normal range as early as 1 month after SCT. Cross-sectional as well as longitudinal analyses revealed no significant correlation between the expression level of FOXP3 mRNA and the occurrence of acute and chronic GVHD. This study suggests that the level of FOXP3+ cells is normal relative to other cell types from the early period after SCT and that their frequency in peripheral blood relative to total leukocytes or T-cells is not indicative of the occurrence of GVHD.
表达Foxp3蛋白的CD4+CD25+调节性T细胞(Treg细胞)在诱导和维持同种异体耐受中发挥重要作用,并且在小鼠模型的同种异体干细胞移植(SCT)后可抑制移植物抗宿主病(GVHD)。因此,阐明人类Treg细胞恢复的动力学及其与GVHD发生的相关性很重要;然而,外周血中Treg细胞频率与GVHD发生之间是否存在相关性仍存在争议。我们通过定量FOXP3信使核糖核酸(mRNA)来检测同种异体SCT后外周血中Treg细胞的恢复情况。除1例患者外,所有患者在SCT后1个月内均实现了完全供体嵌合。FOXP3 mRNA的测量表达水平与内源性对照基因表达水平的比值早在SCT后1个月就迅速恢复到正常范围。横断面分析和纵向分析均显示FOXP3 mRNA表达水平与急性和慢性GVHD的发生之间无显著相关性。本研究表明,SCT后早期相对于其他细胞类型,FOXP3+细胞水平正常,并且其在外周血中相对于总白细胞或T细胞的频率并不能预示GVHD的发生。