T-bet、GATA-3、FoxP3及CD4+CD25+调节性T细胞在AA发病机制中的作用

摘要

Objective To probe into the role of transcription factors T-bet, GATA-3 in the pathogenesis of aplastic a-nemia, and the relationship between CD4+ CD25+ regulatory T cells, transcription factor FoxP3 and the development of aplastic anemia. Methods A total of 27 patients with AA and 25 healthy people (control group ) were selected. The expression of T-bet, GATA-3 and FoxP3 mRNA were detected by Real Time PCR. The expression of T lymphocyte subsets were detected by flow cytometry on peripheral blood mononuclear cell. IFN-y and IL-4 were determined by ELJSA. Results Compared with the control group, the expression of T-bet mRNA in the AA group significantly increased (P <0. 01) , while the expression of GATA-3 and FoxP3 mRNA decreased ( P < 0. 05 or P < 0. 01). The expression of T lymphocyte subsets of CD3+ 、CD3+CD8+ T percentage increased (P<0.05) , while CD3+CD4+ , CD4+CD4+ and the ratio of CD4+ and CDJ decreased (P < 0.05 or P < 0.01). And the level of IFN--y and IFN--y/IL-4 in the AA group were significantly higher than those in control group (P <0.01 ). Conclusions There is functional disorder of T lymphocyte subsets and activation of B lymphocyte proliferation at aplastic anemia. The expression of CD4+ CD25+ regulatory T cells is reduced, and its special transcription factor FoxP3 mRNA is decreased, which indicated that insufficient immunosuppressive effects resulting from the reduction of regulatory T cells may be one important reason the immune imbalance of aplastic anemia.%目的 探讨转录因子T-bet、GATA-3和CD4 CD25调节性T细胞及其转录因子FoxP3在再生障碍性贫血(AA)发病机制中的作用.方法 选择AA患者27例(AA组)、体检健康者25例(对照组),采用RT-PCR技术检测两组外周血单个核细胞(PBMCs)中Th1、Th2细胞及CD4+CD25+调节性T细胞特异性转录因子T-bet、GATA-3、FoxP3 mR-NA的表达,运用流式细胞术检测外周血中T淋巴细胞亚群,ELISA法检测血浆中Th1和Th2类细胞因子IFN-γ、IL-4水平.结果 与对照组相比,AA组的血浆T-bet mRNA相对表达量升高(P＜0.01),GATA-3与FoxP3 mRNA相对表达量降低(P＜0.05,P＜0.01);AA组外周血中CD3+、CD3+ CD8+T细胞占淋巴细胞的百分比较对照组升高(P均＜0.05),CD3+ CD4+、CD4+ CD25+T细胞占淋巴细胞的百分比和CD4+/CD8+值较对照组降低(P＜0.05或P＜0.01)；AA组血浆中IFN-γ水平及IFN-γ/IL-4高于对照组(P均＜0.01).结论 AA患者存在CD4+ CD25+调节性T细胞及其特异性转录因子FoxP3 mRNA表达下调,调节性T细胞的减少及由此引起免疫抑制效应不足可能是AA发生的重要原因之一.