Caspase-1 Activity in CD4 T Cells Is Downregulated Following Antiretroviral Therapy for HIV-1 Infection
Caspase-1 Activity in CD4 T Cells Is Downregulated Following Antiretroviral Therapy for HIV-1 Infection
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DOI：
10.1089/aid.2016.0234
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发表时间：
2017-02-01
影响因子：
1.5
通讯作者：
Lu, Hongzhou
中科院分区：
文献类型：
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作者：
Cai, Rentian;Liu, Li;Lu, Hongzhou
据报道，Caspase 1诱导的细胞死亡和Caspase 3诱导的细胞死亡都是HIV感染中CD4(+) T细胞耗竭的原因。我们通过流式细胞术检测了外周T细胞中与焦亡（Caspase 1）、凋亡（Caspase 3、Caspase 8、Caspase 9）和免疫激活相关的关键蛋白的表达。未经治疗的人类免疫缺陷病毒1 （HIV-1）患者CD4(+) T细胞表达Caspase 1和Caspase 3的百分比显著高于健康对照组（Caspase 1: 19.40% vs. 4.65%, p = 0.006; Caspase 3: 12.75% vs. 4.18%, p < 0.001）。然而，Caspase 3在CD8(+) T细胞中的百分比明显增加，而Caspase 1在CD8(+) T细胞中的百分比没有明显变化（Caspase 1: 3.33% vs. 1.99%, p = 0.821; Caspase 3: 20.35% vs. 4.74%, p < 0.001）。HLA-DR+ CD38(+) CD8(+) T细胞百分比与Caspase 1(+) CD4(+) T细胞百分比呈正相关，与Caspase 3(+) CD4(+) T细胞百分比无显著相关性。在高活性抗逆转录病毒治疗后，表达CD4(+) T细胞的Caspase 1的百分比下降到与健康对照相当的水平（Caspase 1: 6.05% vs. 4.65%, p = 0.514; Caspase 3: 9.67% vs. 4.18%, p < 0.001）。我们的研究表明，CD4(+) T细胞在HIV-1感染中同时经历焦亡和凋亡，而CD8(+) T细胞仅发生凋亡。有效的抗逆转录病毒治疗可以抑制CD4(+) T细胞的焦亡，而不是细胞凋亡。
Both Caspase 1-induced cell death and Caspase 3-induced cell death were reported to be the causes of CD4(+) T cell depletion in HIV infection. We measured by flow cytometry the expression of key proteins associated with pyroptosis (Caspase 1), apoptosis (Caspase 3, Caspase 8, Caspase 9), and immune activation in peripheral T cells. The percentages of CD4(+) T cells that expressed Caspase 1 and Caspase 3 were significantly higher in untreated human immunodeficiency virus 1 (HIV-1) patients compared with healthy control (Caspase 1: 19.40% vs. 4.65%, p = .006; Caspase 3: 12.75% vs. 4.18%, p < .001). However, the percentages of Caspase 3 in CD8(+) T cells increased significantly, while the percentages of Caspase 1 in CD8(+) T cells did not change significantly (Caspase 1: 3.33% vs. 1.99%, p = .821; Caspase 3: 20.35% vs 4.74%, p < .001). The percentages of HLA-DR+ CD38(+) CD8(+) T cells were positively correlated with those of Caspase 1(+) CD4(+) T cells, but not with those of Caspase 3(+) CD4(+) T cells. After highly active antiretroviral therapy, the percentages of Caspase 1, but not of Caspase 3, -expressing CD4(+) T cells decreased to a level comparable with those of healthy controls (Caspase 1: 6.05% vs. 4.65%, p = .514; Caspase 3: 9.67% vs. 4.18%, p < .001). Our study indicated that CD4(+) T cells experience both pyroptosis and apoptosis, while CD8(+) T cells undergo only apoptosis in HIV-1 infection. Pyroptosis, but not apoptosis, in CD4(+) T cells may be inhibited by effective antiretroviral therapy.