调节性T细胞稳态与慢性HIV-1感染引起的异常免疫活化研究

Immune hyperactivation correlated with CD4^+ Foxp3^+ regulatory T cells homeostasis in chronic HIV-1 infection

目的本研究旨在探讨CD4+Foxp3+调节性T细胞(regulatory T cells,Treg)稳态与慢性HIV-1感染者疾病进程及免疫活化的相关性。方法选择50例慢性HIV-1感染者,包括AIDS患者15例(AIDS组)、典型进展(typical progressor,TP)患者25例(TP组)、长期非进展(long-termnon-progressor,LTNP)患者10例(LTNP组),另选健康对照者(healthycontrol,HC)15例(HC组)。用流式细胞仪检测Treg的增殖标志Ki-67和凋亡标志半胱氨酰天冬氨酸蛋白酶-3,同时检测Treg的活化标志CD38和人白细胞抗原-DR。结果在HC组和慢性HIV-1感染者中,Treg的增殖和凋亡速率均显著高于CD4+Foxp3-非调节性T细胞,这种稳态的改变在TP组和AIDS组中更为明显。进一步研究发现Treg增殖和凋亡与其活化程度呈正相关。结论慢性HIV-1感染导致Treg的过度活化,进而导致Treg稳态的改变。Treg稳态可以作为预测HIV/AIDS患者疾病进展的一项指标。

Objective To investigate the correlation of the homeostasis of CD4＋Foxp3＋ regulatory T cells （Treg） with the disease progression and immune activation in patients with chronic HIV-1 infection. Methods Fifty HIV-1-infected subjects including 15 AIDS patients （AIDS group）, 25 typical progressors （TP group）, 10 long-term non-progressors （LTNP group）, and 15 healthy controls （HC group） were enrolled in this study. Treg proliferation and apoptosis from peripheral blood were evaluated by detecting intraeellular Ki-67 and active caspase-3 with flow cytometer, and Treg activation markers, CD38 and human leukocyte antigen-DR were simultaneously monitored. Results In healthy controls and HIV-1-infected patients, Treg cells displayed more increased turnover as indicated by higher expression of proliferation marker Ki-67 and apoptosis marker active caspase-3 than CD4＋Foxp3 non-Treg. Such altered homeostasis occurred more obviously in TP and AIDS groups. Proliferation and apoptosis of Treg cells were positively correlated with immune activation. Conclusions Chronic HIV-1 infection results in Treg hyperactivation, which leads to altered Treg homeostasis during the disease progression. Treg homeostasis may serve as a surrogate marker to predict the disease progression of HIV/AIDS patients.