Memory-biased CD8αα⁺ T cells show reduced abundance and phenotypic remodeling in SLE.

To characterize peripheral CD8αα⁺ T cells in systemic lupus erythematosus (SLE), evaluate their quantitative and phenotypic alterations, and examine associations with autoantibody profiles and inflammatory markers. Forty treatment-naïve SLE patients and 46 age- and sex-matched healthy controls were recruited. Peripheral blood mononuclear cells were analyzed by flow cytometry to quantify CD8αα⁺ and CD8αβ⁺ T-cell subsets, differentiation states (TN, TCM, TEM, TEMRA), and expression of CCR7, CD45RA, CD28, CD27, GZMB, perforin, and GPR56. Correlations with autoantibodies, immunoglobulin levels, complement, and inflammatory markers were assessed. In healthy controls, CD8αα⁺ T cells were less abundant than CD8αβ⁺ T cells and predominantly enriched in central memory (TCM) and terminally differentiated effector memory RA⁺ (TEMRA) subsets, with lower CD28, CD27, CCR7, and GZMB expression. In SLE patients, CD8αα⁺ T cells showed further reductions in absolute counts, decreased CD28, and increased GZMB and GPR56, while differentiation subset distribution remained unchanged. Alterations in CD8αα⁺ T-cell counts and marker expression correlated with autoantibody titers, immunoglobulin levels, complement C4, and inflammatory indices. Peripheral CD8αα⁺ T cells form a distinct memory-enriched subset that is numerically reduced and phenotypically remodeled in SLE. Their quantitative and phenotypic alterations correlate with immunological and inflammatory parameters.