Yin Xiao-Xiao, Liu Chuan-Fang, Li Li-Zhen, Chen Wei-Zhi
Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China.
Zhonghua Xue Ye Xue Za Zhi. 2008 May;29(5):308-11.
To quantify the CD4+ CD25+ CD127(low) regulatory T cell (Treg), the expression levels of forkhead/winged helix transcription factor FOXP3 and Notch1 mRNA in aplastic anemia (AA) patients before and after treatment, and explore the significance of Treg in pathogenesis of AA.
CD4+ CD25+ and CD4+ CD25+ CD127(low) T cells in peripheral blood were examined with FACS in 29 AA patients at active phase, 14 at recovery phase, 11 at unrecovery phase, and 15 normal controls. The levels of FOXP3 mRNA and Notch1 mRNA expression were detected with RT-PCR, and the correlations between Treg, FOXP3 mRNA and Notchl mRNA were analyzed.
The percentages of peripheral activated CD4+ CD25+ T cells in AA patients at active phase (4.3 +/- 0.7)% and unrecovery phase (4.2 +/- 0.6)% were significantly higher than those in normal controls (2.4 +/- 0.8)% (P < 0.05). The proportion of these cells in AA patients at recovery phase was reduced to (2.6 +/- 0.7)% (P < 0.05), being no difference from that in control group. The number of CD4+ CD25+ CD127(low) T cells in AA patients at active phase (2.4 +/- 1.2)% and unrecovery phase (2.5 +/- 1.1)% was decreased significantly compared with those in normal controls (7.1 +/- 2.7)% (P < 0.01) and in AA patients at recovery phase (5.3 +/- 1.0)% (P < 0.01), there was no difference between the latter two groups. In active phase AA patients, the levels of FOXP3 mRNA and Notchl mRNA (0.260 +/- 0.011 and 0.018 +/- 0.005, respectively) were lower than that in control group (1.307 +/- 0.011 and 0.308 +/- 0.028, respectively) (P < 0.01 and P < 0.01). After treatment, the levels significantly increased to 1.287 +/- 0.012 and 0.281 +/- 0.013 (P < 0.01 and P < 0.01), but there was no difference with that of normal controls (P > 0.05). CD4+ CD25+ CD2(low) T cells and FOXP3 were positively related with Notchl (P < 0.01) in AA patients.
The decreased number and suppressive activity of CD4 CD25+ CD127(low) Treg cells in the peripheral blood of AA patients cause over-activation of autoreactive T cells and suppression of haematopoiesis. One of the mechanisms maybe the reduced expression of Notch1 in the target cells.
定量分析再生障碍性贫血（AA）患者治疗前后外周血中CD4+ CD25+ CD127（低表达）调节性T细胞（Treg）、叉头/翼状螺旋转录因子FOXP3及Notch1 mRNA的表达水平，探讨Treg在AA发病机制中的意义。
采用流式细胞术检测29例活动期AA患者、14例恢复期AA患者、11例未缓解期AA患者及15名正常对照者外周血中CD4+ CD25+及CD4+ CD25+ CD127（低表达）T细胞。采用逆转录聚合酶链反应（RT-PCR）检测FOXP3 mRNA及Notch1 mRNA表达水平，并分析Treg、FOXP3 mRNA与Notch1 mRNA之间的相关性。
活动期（4.3±0.7）%及未缓解期（4.2±0.6）% AA患者外周血活化CD4+ CD25+ T细胞百分比显著高于正常对照者（2.4±0.8）%（P<0.05）。恢复期AA患者该细胞比例降至（2.6±0.7）%（P<0.05），与对照组无差异。活动期（2.4±1.2）%及未缓解期（2.5±1.1）% AA患者CD4+ CD25+ CD127（低表达）T细胞数量显著低于正常对照者（7.1±2.7）%（P<0.01）及恢复期AA患者（5.3±1.0）%（P<0.01），后两组间无差异。活动期AA患者FOXP3 mRNA及Notch1 mRNA水平（分别为0.260±0.011及0.018±0.005）低于对照组（分别为1.307±0.011及0.308±0.028）（P<0.01及P<0.01）。治疗后，上述水平显著升高至1.287±0.012及0.281±0.013（P<0.01及P<0.01），但与正常对照者无差异（P>0.05）。AA患者中，CD4+ CD25+ CD127（低表达）T细胞及FOXP3与Notch1呈正相关（P<0.01）。
AA患者外周血中CD4+ CD25+ CD127（低表达）Treg细胞数量及抑制活性降低，导致自身反应性T细胞过度活化及造血抑制。其机制之一可能是靶细胞中Notch1表达降低。
