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 p16INK4a 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 p16INK4a was assessed by qPCR. The SLE-CI group demonstrated a higher CD4⁺/CD8⁺ inverted ratio and increased p16INK4a 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.