重型再生障碍性贫血患者骨髓中辅助性T细胞亚群数量及功能的变化

Quantitative and functional changes of T helper cell subsets in the bone marrow of severe aplastic anemia patients

目的 研究重型再生障碍性贫血 (SAA)患者在免疫抑制治疗 (IST)恢复前后骨髓中辅助性T细胞 (Th细胞 )亚群改变情况及与造血功能的关系。方法 以流式细胞仪测定 2 4例发病期、15例恢复期SAA患者及 16名正常对照者骨髓中Th细胞亚群及CD3+ CD8+ 细胞改变情况 ;以放射免疫法测定 2 0例发病期SAA患者、12例IST后恢复期患者及 16名正常对照者血清中TNF α、IL 4水平 ;评价Th1与CD3+ CD8+ 细胞、TNF α的相关关系 ;评价Th1、CD3+ CD8+ 细胞、TNF α、IL 4及Th1/Th2平衡与网织红细胞、中性粒细胞绝对值的相关关系。结果 正常对照组骨髓中Th1细胞、Th2细胞百分率及Th1/Th2比值分别为 (0 .4 2± 0 .30 ) %、(0 .2 4± 0 .17) %、1.5 7± 0 .93;发病期SAA分别为 (4 .87± 2 .6 4 ) %、(0 .4 1±0 .2 6 ) %、2 1.2 2± 5 .0 7,均显著多于正常对照 (P <0 .0 1,P <0 .0 5 ,P <0 .0 1) ,恢复期分别为 (0 .5 3± 0 .2 2 ) %、(0 .4 4± 0 .15 ) %、1.38± 0 .4 5 ,与正常对照组相当 (P均 >0 .0 5 ) ;CD3+ CD8+ 细胞亦由发病期的(32 .32± 18.6 9) %显著下降为 (13.76± 2 .96 ) % (P <0 .0 1) ;SAA发病期血清中TNF α、IL 4为 (4 .2 9± 3.15 ) μg/L、(1.2 4± 0 .73) μg/L ,高于正常对照组的 (1.2 1± 1.16 )

Objective To evaluate the quantitative and functional changes of T helper (Th) cell subsets in the bone marrow of severe aplastic anemia (SAA) patients and the relationship between these changes and the patients hematopoietic function. Methods By FACS, the quantity and ratio of Th1 and Th2 cells, the percentage of CD3^+CD8^+ cells in the bone marrow were detected in 24 patients with SAA at active phase, 15 patients with SAA at recovery phase, and 16 normal controls. By radioimmunoassay, the serum levels of TNF-α, or IL-4 in 20 SAA patients at active phase, 12 at recovery phase and 16 normal controls were measured. The relationships between CD3^+CD8^+ cells, TNF-α and Ret, ANC; and between Th1 cells and CD3^+CD8^+ cells, TNF-α or Ret, ANC; between IL-4, balance of Th1/Th2 and Ret, ANC were evaluated. Results The percentages of Th1 and Th2 cells, and ratio of Th1/Th2 in bone marrow of SAA patients at active phase were (4.87±2.64)%,(0.41±0.26)% and 21.22±5.07,respectively,being higher than those of normal controls [(0.42±0.30)% (P<0.01),(0.24±0.17)% (P<0.05) and (1.57±0.93)(P<0.01),respectively] and all of them reduced to normal levels of SAA at recovery phase (P>(0.05)). The percentage of CD3^+CD8^+ cells significantly decreased from (32.32±8.69)% at active phase to (13.76±2.96)% at recovery phase (P<0.01). The serum levels of TNF-α and IL-4 at active phase was ((4.29)±3.15) μg/L and (1.24±0.73) μg/L,respectively, being higher than those of normal controls((1.21)±(1.16)) μg/L, (1.18±0.97) μg/L, but only the difference of TNF-α was statistically significant ((P<)(0.01)). In recovery SAA patients, the serum levels of TNF-α significantly decreased to (1.46±1.41)μg/L ((P<)0.01), and the levels of IL-4 increased markedly to (3.05±1.94) μg/L. The CD3^+CD8^+ cells and TNF-α of patients negatively correlated with Ret (P<0.05;P<0.05) and ANC (P<0.05;P<0.05), Th1 cells correlated with CD3^+CD8^+ cells and TNF-α positively (P<0.01;P<0.05), the Ret and ANC negatively(P<0.01;P<0.01), IL-4 and the balance of Th1/Th2 positively correlated with Ret and ANC (P<0.05,P<0.01;P<0.01,P<0.01). Conclusion The bone marrow failure in SAA might be caused not only by the increase of Th1 cells, Th1 type effector cells and cytokines, but also by unsufficient compensation of Th2 cells and Th2 type cytokines, which shifted the balance of Th1/Th2 favorable to Th1.