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目的探讨CD4+调节性T细胞(Tregul atory,Treg)在再生障碍性贫血(aplasticanemia,AA)免疫发病机制中的作用。方法对2005年7月至2006年3月苏州大学附属第一医院23例发病期AA患者、10例恢复期AA患者及15名正常对照者测定骨髓中CD4+CD25+Treg、CD4+CTLA-4+Treg、CD4+PD-1+Treg、CD3+CD8-IL-10+Treg、CD3+CD8-TGF-β1+Treg、CD3+CD8-IL-4+Treg变化,分析其与免疫启动因素CD28及免疫效应因素干扰素-γ(IFN-γ)的关系。结果AA发病期、恢复期及正常对照组CD4+CD25+Treg数比较差异无显著性意义;AA发病期CD4+CTLA-4+Treg表达较对照组明显下降,PD-1与对照组比较差异无显著性意义;AA恢复期CD4+CT-LA-4+Treg及PD-1表达均较发病期明显升高,与对照组相当;AA恢复期患者IFN-γ较发病期明显下降(P=0.021),与正常对照组相当(P=0.402),IL-4、TGF-β及IL-10与AA发病组及对照组比较差异均无显著性意义;AA发病期患者骨髓CD3+CD4+T淋巴细胞膜表面CD28表达较正常对照组明显增加;AA恢复期患者的CD28表达率较发病期显著降低,亦低于正常对照组(P=0.048)。AA发病期CD4+CTLA-4+Treg明显下降,其余Treg无显著变化;AA恢复期CD4+CTLA-4+Treg、CD4+PD-1+Treg升高显著。CD28/CTLA-4、CD28/PD-1发病期与对照组比,均显著升高;AA恢复期为明显低于发病期,与对照组相当。IFN-γ+/IL-4+、IFN-γ+/TGF-β+及IFN-γ+/IL-10+发病期较对照组均显著升高;AA恢复期明显低于发病期,而与对照组相当。结论在免疫应答起始阶段或效应阶段,AA正性调控共刺激因子表达增加,而负性调控共刺激因子表达减少或无变化,使免疫平衡向持续增强偏移,调节性因素增高利于造血恢复;对于增强的免疫应答,AA的CD4+Treg呈下降趋势,可能与发病有关。
Objective To investigate the role of CD4 + regulatory T cells (Tregs) in the pathogenesis of aplastic anemia (AA). Methods The serum levels of CD4 + CD25 + Treg and CD4 + CTLA-4 in bone marrow from 23 patients with AA in the first affiliated hospital of Soochow University from July 2005 to March 2006, 10 patients with convalescent AA and 15 normal controls were measured. Treg, CD4 + PD-1 + Treg, CD3 + CD8-IL-10 + Treg, CD3 + CD8-TGF-β1 + Treg and CD3 + CD8-IL-4 + Treg. Immune effector factor interferon-γ (IFN-γ) relationship. Results There was no significant difference in the number of CD4 + CD25 + Tregs between AA and convalescent and normal control groups. The expression of CD4 + CTLA-4 + Treg in AA group was significantly lower than that in control group at the onset of AA, but no difference was found between PD-1 and control group The expression of CD4 + CT-LA-4 + Treg and PD-1 in convalescent phase of AA were significantly higher than that of the control group, while the level of IFN-γ in AA convalescent phase was significantly lower than that of the convalescent phase (P = 0.021 ) And normal control group (P = 0.402), IL-4, TGF-β and IL-10 and AA pathogenesis group and the control group showed no significant difference; AA incidence of patients with bone marrow CD3 + CD4 + T lymphocytes The expression of CD28 on the cell membrane surface was significantly higher than that in the normal control group. The expression of CD28 in AA convalescent stage was significantly lower than that in the onset stage and lower than that in the normal control group (P = 0.048). The incidence of CD4 + CTLA-4 + Treg was significantly decreased during the onset of AA, while the other Tregs showed no significant changes. The levels of CD4 + CTLA-4 + Treg and CD4 + PD-1 + Tregs were significantly increased during AA recovery. CD28 / CTLA-4, CD28 / PD-1 incidence of the control group compared with the significantly increased; AA recovery period was significantly lower than the onset, and the control group. The incidence of IFN-γ + / IL-4 +, IFN-γ + / TGF-β + and IFN-γ + / IL-10 + was significantly higher than that of the control group The control group is quite. Conclusion In the initial stage or effector stage of immune response, the positive expression of AA co-stimulatory factor is increased, while the expression of negative regulatory co-stimulatory factor is decreased or unchanged, the immune balance is continuously increased and the regulatory factors are increased, which is beneficial to hematopoietic recovery ; For the enhanced immune response, AA CD4 Tregs showed a downward trend, which may be related to the pathogenesis.