Immunosenescent and exhausted T cells in systemic lupus erythematosus patients with cognitive impairment

The objective was to assess the expression of senescence and exhaustion markers in CD4⁺ and CD8⁺ T-cell subsets, along with the p16^INK4a gene, in patients with systemic lupus erythematosus (SLE) and cognitive impairment (CI), compared with SLE patients without CI and healthy controls (HC). All participants underwent a standardized neurocognitive test battery, and CI was defined as performance ≥2 SD below the normative mean in ≥1 cognitive domain. The expression of immunosenescence and exhaustion markers was assessed by flow cytometry; expression of p16^INK4a was assessed by qPCR. The SLE-CI group demonstrated a higher CD4⁺/CD8⁺ inverted ratio and increased p16^INK4a expression. Compared with both SLE patients without CI and HC, SLE-CI patients exhibited reduced expression of CTLA-4⁺, LAG-3⁺, and PD-L1⁺ on CD4⁺ T-cells, as well as decreased PD-L1⁺ and TIM-3⁺ expression on CD8⁺ T-cells. Immunosenescence and T-cell exhaustion may contribute to the pathogenesis of CI in SLE.