Bmi-1 Regulates Autoreactive CD4+ T Cell Survival in Immune Thrombocytopenia Patients
Bmi-1 Regulates Autoreactive CD4+ T Cell Survival in Immune Thrombocytopenia Patients
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DOI：
10.1007/s10875-011-9643-2
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发表时间：
2012-02
影响因子：
9.1
通讯作者：
Li Ma;Zeping Zhou;Donglei Zhang;Hongmei Wang;Huiyuan Li;F. Xue;R. Yang
中科院分区：
文献类型：
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作者：
Li Ma;Zeping Zhou;Donglei Zhang;Hongmei Wang;Huiyuan Li;F. Xue;R. Yang
免疫性血小板减少症(ITP)患者的自身反应性T细胞经历快速克隆性扩增，并抵抗凋亡以维持其在血小板减少症中的持续作用。由于Bmi-1与记忆性CD4+T细胞的存活和Th2的增殖有关，我们推测Bmi-1可能在ITP患者自身反应性的CD4+T细胞克隆性增殖和Th1/Th2的发展中起作用。研究发现，活动期ITP患者外周血中BMI-1的表达高于缓解期和健康对照组，自身反应性的CD4+T细胞具有更强的增殖能力和抗凋亡能力。我们评价了Bmi-1在ITP自身反应性CD4+T细胞增殖和Th1偏向状态中的作用。我们使用含有Bmi-1和shBmi-1的慢病毒转移载体在自体血小板刺激过程中感染ITP患者和健康对照组的CD4+T细胞。采用流式细胞仪和酶联免疫吸附试验检测各项指标。结果表明，短发夹状RNA抑制BMI-1可抑制ITP患者自身反应性CD4+T细胞的增殖，增加其凋亡率。正常人外周血中BMI-1的表达增加，促进了CD4+T细胞的增殖，抑制了其凋亡。BMI-1可显著促进CD4+T细胞分泌IL-4。提示BMI-1在ITP患者自身反应性CD4+T细胞增殖能力和抗凋亡能力中起一定作用。
Autoreactive T cells in immune thrombocytopenia (ITP) patients undergo a rapid clonal expansion and are resistant to apoptosis to maintain continuous effect in thrombocytopenia. As Bmi-1 is involved in memory CD4+T cell survival and Th2 proliferation, we hypothesized that Bmi-1 may have a role in autoreactive CD4+T cell clonal expansion and Th1/Th2 development in ITP patients. We found that CD4+T cells from active ITP patients had a higher Bmi-1 expression in comparison with remission and healthy controls, and autoreactive CD4+T cells had more capability to proliferate and resistance to apoptosis than that of healthy controls. We evaluated the part that Bmi-1 played in proliferation and Th1 bias condition of autoreactive CD4+T cells in ITP. We used lentiviral transfer vectors containing Bmi-1 and shBmi-1 to infect CD4+T cells from ITP patients and healthy controls during autologous platelets stimulation. Flow cytometry and ELISA were applied to detect various parameters. The results showed that suppression of Bmi-1 using short hairpin RNA inhibited the platelet-mediated proliferation and increased apoptosis of autoreactive CD4+T cells from ITP patients. Increased Bmi-1 expression in CD4+T cells from healthy controls promoted the proliferation and inhibited apoptosis of CD4+T cells. Bmi-1 significantly promoted interleukin-4 secretion by CD4+T cells. These findings suggest that Bmi-1 plays a part in autoreactive CD4+T cell proliferative capability and apoptotic resistance in ITP patients.