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

[Quantitative and functional changes of T helper cell subsets in the bone marrow of severe aplastic anemia patients].
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重症再生障碍性贫血患者骨髓中T辅助细胞亚群数量及功能的变化

DOI:
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发表时间:
2004
影响因子:
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通讯作者:
Chong
Chong
中科院分区:
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文献类型:
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作者:
G. He;Z. Shao;Hong He;Hong Liu;J. Bai;Jun Shi;Yan;M. Tu;Juan Sun;H. Jia;Chong

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目的 目的探讨重型再生障碍性贫血(SAA)患者骨髓辅助性T细胞(Th)亚群数量和功能的变化及其与造血功能的关系。 方法 采用流式细胞仪检测24例活动期SAA患者、15例恢复期SAA患者和16例正常对照者骨髓中Th 1/Th 2细胞数量、比例、CD 3 + CD 8+细胞百分率。采用放射免疫法测定20例SAA患者活动期、12例SAA患者恢复期及16例正常人血清TNF-α、IL-4水平。分析CD 3(+)CD 8(+)细胞、TNF-α与Ret、ANC的关系,Th 1细胞与CD 3(+)CD 8(+)细胞、TNF-α或Ret、ANC的关系,IL-4、Th 1/Th 2平衡与Ret、ANC的关系。 结果 SAA患者活动期骨髓Th 1、Th 2细胞百分比及Th 1/Th 2比值分别为(4.87 +/- 2.64)%,(0.41 ± 0.26)%和21.22 ± 5.07,均高于正常对照组。(0.42 ± 0.30)%(P < 0.01),(0.24 ± 0.17)%(P < 0.05)和(1.57 ± 0.93)%(P < 0.01),恢复期SAA均降至正常水平(P > 0.05)。CD 3(+)CD 8(+)细胞百分比由活动期的(32.32 ± 8.69)%降至恢复期的(13.76 ± 2.96)%(P < 0.01)。活动期血清TNF-α和IL-4水平(4.29 +/- 3.15)微克/升,(1.24 ± 0.73)μ g/L,高于正常对照组(1.21 ± 1.16)μ g/L,(1.18 ± 0.97)μ g/L,但只有TNF-α差异有统计学意义(P < 0.01)。SAA恢复期患者血清TNF-α水平显著下降至(1.46 ± 1.41)μ g/L(P < 0.01),IL-4水平显著升高至(3.05 ± 1.94)μ g/L。CD 3(+)CD 8(+)细胞和TNF-α与Ret呈负相关(P < 0.05; P < 0.05)和ANC Th 1细胞与CD 3(+)、CD 8(+)细胞、TNF-α呈正相关(P <0.05; P < 0.05 Ret与ANC呈负相关(P <0.01; P <0.01),IL-4、Th 1/Th 2平衡与Ret、ANC呈正相关(P < 0.05,P < 0.01; P <0.01,P < 0.01)。 结论 SAA患者骨髓功能衰竭不仅与Th 1细胞、Th 1型效应细胞和细胞因子增多有关,还与Th 2细胞和Th 2型细胞因子代偿不足,使Th 1/Th 2平衡向Th 1方向倾斜有关。
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-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. 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-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). 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 insufficient compensation of Th2 cells and Th2 type cytokines, which shifted the balance of Th1/Th2 favorable to Th1.