Caspase-1 Activity in CD4 T Cells Is Downregulated Following Antiretroviral Therapy for HIV-1 Infection

Abstract

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.