The CD4/CD8 ratio is associated with T lymphocyte functions in long-term virally suppressed patients with HIV
Qing Xiao, Fengting Yu, Liting Yan, Xiaojie Lao, Xuelei Liang, Hongxin Zhao, Liuyue Zhai, Zailin Yang, Xiaomei Zhang, Yao Liu, Fujie Zhang
Abstract
Abstract Objective Long-term management of people living with HIV (PLWHs) often relies on CD4 + T cell counts for assessing immune recovery, yet a single metric offers limited information. This study aimed to explore the association between the CD4/CD8 ratio and T lymphocyte activities in PLWHs. Methods 125 PLWHs and 31 HIV-uninfected controls (UCs) were enrolled and categorized into four groups based on their CD4/CD8 ratios: extremely low ratio (ELR) group: 0.4 < CD4/CD8; low ratio (LR) group: 0.4 ≤ CD4/CD8<0.7; medium ratio (MR) group: 0.7 ≤ CD4/CD8<1; high ratio (HR) group: CD4/CD8 ≥ 1. The activation and proliferation phenotypes, mitochondrial functions, and inflammatory indexes of CD4 + T cells and CD8 + T cells were measured, and correlations between the CD4/CD8 ratio and T cell functions were analyzed. Results T cell activation and proliferation were significantly elevated in the ELR group compared to UCs. However, the ELR group had a larger proportion of T cells with lipid peroxidation, mitochondrial lipid reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) abnormalities compared to the other groups. As the CD4/CD8 ratio increased, mitochondrial lipid peroxidation damage decreased and MMP was restored. Additionally, the ELR group had more inflammatory markers in CD4 + T cells. Correlation analysis revealed that the CD4/CD8 ratio was associated with multiple T cell functions, and its correlation coefficient with mitochondrial function was higher than that of CD4 + T cell count. Conclusion The CD4/CD8 ratio is closely related to T lymphocyte functions and is significantly superior to the CD4 + T cell count in reflecting the mitochondrial lipid peroxidation level and mitochondrial functions within T lymphocytes.