P-Selectin Glycoprotein Ligand (PSGL)-1 Expression on CD4+ T Cells in Patients with HIV: Insights from an Observational Study

In the context of HIV infection, PSGL-1 expression and impact on CD4⁺ T cells remain largely unexplored. Thus, to address these critical gaps in knowledge, blood was sampled from HIV-negative controls and both ART-treated and ART-naïve individuals and stratified according to CD4⁺ T cell counts. PSGL-1 expression on CD4⁺ T cells and CD4⁺ T cell-platelet aggregates, along with PD-1, Bcl-2, and Caspase-3, were assessed with flow cytometry. Levels of IL-12, IFN-γ, LPS, and β-glucan were determined with ELISA. Spearman's correlation test was used to determine the correlation between PSGL-1 expression on CD4⁺ T cell counts and markers of inflammation/translocation. PSGL-1 was significantly overexpressed in ART-treated individuals (<i>p</i> < 0.0001) and exhibited markedly lower expression in ART-naïve individuals (<i>p</i> ≤ 0.01), consistent with a suppressive influence of HIV VL prior to ART initiation and a proinflammatory environment promoting PSGL-1 overexpression during ART. In both groups, individuals with CD4⁺ T cells < 200 cells/µL exhibited elevated levels of PSGL-1 (<i>p</i> < 0.05) and increased CD4⁺ T cell-platelet aggregates (<i>p</i> < 0.05). In ART-treated individuals only, PSGL-1 expression positively correlated with IFN-γ (r = 0.318, <i>p</i> = 0.021), IL-12 (r = 0.498, <i>p</i> < 0.001), LPS (r = 0.382, <i>p</i> = 0.005), and β-glucan (r = 0.318, <i>p</i> = 0.021), reinforcing the link between inflammatory activation and PSGL-1 overexpression. In this group, those with CD4⁺ T cells < 200 cells/µL had higher Caspase-3 and PD-1 (<i>p</i> < 0.0001) and lower Bcl-2 (<i>p</i> ≤ 0.01). No significant differences in these markers were found across CD4⁺ strata in ART-naïve individuals. PSGL-1 expression is influenced by ART and immune status. PSGL-1 signaling drives CD4⁺ T cell phenotypic changes.