慢性HIV-1感染者CD8细胞的铁死亡特点及其临床意义

Characteristics and clinical implications of ferroptosis of CD8 T cells in patients with chronic HIV-1 infection

目的 分析慢性HIV-1感染者外周血中CD8细胞的铁死亡水平,探讨CD8细胞铁死亡的临床意义。方法 利用流式细胞术检测HIV-1感染者和健康对照者外周血中CD8细胞的脂质过氧化水平,分析不同疾病状态下HIV-1感染者CD8细胞的不同记忆分化亚群及CXCR5+CD8细胞和CXCR3+CD8细胞的铁死亡情况,探究其变化特点及与疾病进展的关系。结果 纳入符合标准的30例未经ART的HIV-1感染者(TN),ART大于两年的免疫应答者(IR)17例,免疫无应答者(INR)9例与13例健康对照(HC),分析发现HC组和IR组相比TN组的CD8细胞的脂质过氧化水平显著升高(中位数TN vs. HC,0.068 85 vs. 0.041 16,P=0.000 8;TN vs. IR,0.068 85 vs. 0.045 06,P=0.001 6)。TN组CD8细胞EM亚群的脂质过氧化水平高于CM亚群、Naive亚群和EMRA亚群(中位数EM vs. CM vs. Na?ve vs.EMRA:0.083 14 vs. 0.061 19 vs. 0.071 27 vs. 0.063 09)。在TN组中,CXCR5+CD8细胞的脂质过氧化水平显著高于CXCR5-CD8细胞(中位数0.082 65 vs. 0.068 75, P<0.000 1),CXCR3+CD8细胞显著低于CXCR3-CD8细胞(中位数0.065 68 vs. 0.072 80,P<0.000 1)。TN组的CD8细胞脂质过氧化水平与CD4细胞计数具有显著负相关性(r=-0.470 1,P=0.008 8)。结论 在未经ART的HIV-1感染者中CD8细胞的铁死亡水平显著升高,其铁死亡水平与CD4细胞计数显著负相关,暗示了CD8细胞的铁死亡与HIV-1感染后的疾病进展程度有关。

Objective To clarify the ferroptosis of peripheral blood CD8 T cells in HIV-1 infected patients,and to explore its clinical significance.Methods Lipid peroxidation of peripheral blood CD8 T cells in HIV-1 infected patients and healthy controllers was detected by flow cytometry.For HIV-1 infected patients with different disease stages,the ferroptosis situation of different memory differentiation subgroups of CD8 T cells,CXCR5+CD8 T cell,and CXCR3*CD8 T cells were analyzed,and the correlation between changing characteristics of CD8 T cell and the disease progression was explored.Results 30 treatment-naive HIV-1 infected patients(TN),17 immunological responders(IR)with successful antiviral therapy(ART),9 immunological non-responders(INR),and 13 healthy controls(HC)were enrolled.Compared to HC and IR,the lipid peroxidation of CD8 T cells in TN was significantly increased(median TN vs HC:0.06885 vs.0.04116,P=0.0008;TN vs IR:0.06885 vs.0.04506,P=0.0016).The lipid peroxidation of EM subgroup in TN was higher than CM,Naive,and EMRA subgroups(median EM vs.CM vs.Naive vs.EMRA:0.08314 vs.0.06119 vs.0.07127 vs.0.06309).In TN,the lipid peroxidation of CXCR5+CD8 T cells was significantly higher than CXCR5°CD8 T cells(median 0.08265 vs.0.06875,P<0.0001),while the lipid peroxidation of CXCR3+CD8 T cells was significantly lower than CXCR3°CD8 T cells(median 0.06568 vs.0.07280,P<0.0001).The lipid peroxidation of CD8 T cell in TN was negatively correlated with CD4 T cell count(r=-0.4701,P=0.0088).Conclusions In treatment-naive HIV-1 infected patients,ferroptosis of CD8 T cells is significantly increased,which is positively correlated with disease progressin.It suggests that ferroptosis of CD8 T cells plays an important role in the disease progression of HIV-1 infection.