He Guang-sheng, Shao Zong-hong, He Hong, Liu Hong, Bai Jie, Shi Jun, Cao Yan-ran, Tu Mei-feng, Sun Juan, Jia Hai-rong, Yang Chong-li
Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2004 Oct;25(10):613-6.
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.
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-alpha, 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-alpha and Ret, ANC; and between Th1 cells and CD3(+)CD8(+) cells, TNF-alpha or Ret, ANC; between IL-4, balance of Th1/Th2 and Ret, ANC were evaluated.
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-alpha and IL-4 at active phase was (4.29 +/- 3.15) microg/L and (1.24 +/- 0.73) microg/L, respectively, being higher than those of normal controls (1.21 +/- 1.16) microg/L, (1.18 +/- 0.97) microg/L, but only the difference of TNF-alpha was statistically significant (P < 0.01). In recovery SAA patients, the serum levels of TNF-alpha significantly decreased to (1.46 +/- 1.41) microg/L (P < 0.01), and the levels of IL-4 increased markedly to (3.05 +/- 1.94) microg/L. The CD3(+)CD8(+) cells and TNF-alpha 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-alpha 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).
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 insufficient compensation of Th2 cells and Th2 type cytokines, which shifted the balance of Th1/Th2 favorable to Th1.
评估重型再生障碍性贫血(SAA)患者骨髓中辅助性T(Th)细胞亚群的数量和功能变化,以及这些变化与患者造血功能之间的关系。
采用流式细胞术(FACS)检测24例急性期SAA患者、15例恢复期SAA患者和16例正常对照者骨髓中Th1和Th2细胞的数量及比例,以及CD3(+)CD8(+)细胞的百分比。采用放射免疫分析法检测20例急性期SAA患者、12例恢复期SAA患者和16例正常对照者血清中肿瘤坏死因子-α(TNF-α)或白细胞介素-4(IL-4)的水平。评估CD3(+)CD8(+)细胞、TNF-α与网织红细胞(Ret)、中性粒细胞绝对值(ANC)之间的关系;Th1细胞与CD3(+)CD8(+)细胞、TNF-α或Ret、ANC之间的关系;IL-4、Th1/Th2平衡与Ret、ANC之间的关系。
急性期SAA患者骨髓中Th1和Th2细胞的百分比及Th1/Th2比值分别为(4.87±2.64)%、(0.41±0.26)%和21.22±5.07,均高于正常对照者[(0.42±0.30)%(P<0.01)、(0.24±0.17)%(P<0.05)和(1.57±0.93)(P<0.01)],且在恢复期SAA患者中均降至正常水平(P>0.05)。CD3(+)CD8(+)细胞的百分比从急性期的(32.32±8.69)%显著降至恢复期的(13.76±2.96)%(P<0.01)。急性期患者血清中TNF-α和IL-4水平分别为(4.29±3.15)μg/L和(1.24±0.73)μg/L,高于正常对照者(1.21±1.16)μg/L、(1.18±0.97)μg/L,但仅TNF-α的差异有统计学意义(P<0.01)。在恢复期SAA患者中,血清TNF-α水平显著降至(1.46±1.41)μg/L(P<0.01),而IL-4水平显著升至(3.05±1.94)μg/L。患者的CD3(+)CD8(+)细胞和TNF-α与Ret(P<0.05;P<0.05)和ANC(P<0.05;P<0.05)呈负相关,Th1细胞与CD3(+)CD8(+)细胞和TNF-α呈正相关(P<0.01;P<0.05),与Ret和ANC呈负相关(P<0.01;P<0.01),IL-4和Th1/Th2平衡与Ret和ANC呈正相关(P<0.05,P<0.01;P<0.01,P<0.01)。
SAA患者的骨髓衰竭可能不仅是由于Th1细胞、Th1型效应细胞和细胞因子增加,还可能是由于Th2细胞和Th2型细胞因子补偿不足,导致Th1/Th2平衡向Th1偏移。