CD8⁺ Regulatory T Cell Deficiency in Elderly-Onset Rheumatoid Arthritis

Elderly-onset rheumatoid arthritis (EORA) is associated with higher disease activity and accelerated joint destruction compared with young-onset RA (YORA). However, the underlying immunological mechanism remains unclear. Regulatory T cells (Tregs) are an immunosuppressive T cell subset, and CD4⁺ Tregs are deficient and/or dysfunctional in RA; however, CD8⁺ Tregs have not been fully examined in RA. Here, we aimed to determine the role of CD8⁺ Tregs, particularly in EORA. A total of 40 patients (EORA, n = 17; YORA, n = 23) were cross-sectionally enrolled. Current disease activity and treatment were comparable between the two groups; however, levels of multiple cytokines, including IL-1β, TNFα, interferon (IFN)-γ, IL-2, and IL-10, were significantly increased in EORA. The number of CD4⁺ Tregs did not differ between the groups (p = 0.37), but those of CD8⁺ Tregs were significantly decreased in EORA (p = 0.0033). The number of CD8⁺ Tregs were inversely correlated with plasma matrix metalloprotease (MMP)-3 levels (r = -0.3331, p = 0.036). Our study results revealed an intrinsic deficiency of CD8⁺ Tregs in patients with EORA, which leaves synovitis unchecked with excessive MMP-3 release. A therapeutic approach to restore CD8⁺ Tregs may provide a new avenue for the treatment of EORA.