Abstract / Summary
Abstract Background and Objective: Cytomegalovirus (CMV) seropositivity has been associated with lower susceptibility to multiple sclerosis (MS), although the immunological mechanisms underlying this relationship remain unclear. CMV profoundly remodels the natural killer cell receptor (NKR) repertoire of NK cells, but its impact on T cells and its interplay with aging in MS are less well characterized. We aimed to characterize CMV-related changes in NKR expression on T cells and investigate their relationship with aging and clinical variables in MS. Methods In this multicenter cross-sectional study, 280 patients with MS and 50 healthy controls underwent peripheral blood immunophenotyping by flow cytometry. NKR expression on CD8 + and CD4 + T cells was analyzed according to CMV serostatus. Associations between NKR expression, age, and MS clinical variables were assessed using correlation and multivariable linear regression analyses. Results CMV seropositivity was associated with higher proportions of LILRB1-expressing CD8 + T cells in both patients with MS and controls. In patients with MS, LILRB1 expression correlated with age and, among CMV-seropositive individuals, positively with disease duration and inversely with annualized relapse rate. LILRB1 expression also correlated with loss of CD27/CD28 in CD8 + T cells, consistent with terminal differentiation. After multivariable adjustment, CMV seropositivity (β = 9.8; 95% CI, 5.8–14; p < 0.001) and age (β = 0.40; 95% CI, 0.19–0.62; p < 0.001) were independently associated with higher proportions of LILRB1-expressing CD8 + T cells. Conclusion CMV seropositivity and aging are independently linked to increased LILRB1 expression on CD8 + T cells in MS. These findings suggest that persistent CMV-related immune remodeling may contribute to age-associated changes in adaptive immunity in MS and potentially to the shift toward lower inflammatory disease activity observed with advancing age.