Characterization of effector memory CD8⁺ T cells in the synovial fluid of rheumatoid arthritis

Little is known about the cellular characteristics of CD8⁺ Tcells in rheumatoid arthritis (RA).We addressed this by investigating whether the frequency of the CD8⁺ T cell subsets and their phenotypic characteristics are altered in the peripheral blood and synovial fluid (SF) from patients with RA. In this study, CD8⁺ T cells, mainly CD45RA-effector memory (EM) CD8⁺ T cells, were increased significantly in the SF, but not in the peripheral blood from RA patients, compared with healthy controls. The synovial EM CD8⁺ T cells were activated phenotypes with high levels of CD80, CD86, and PD-1, and had a proliferating signature in vivo upon Ki-67 staining, whereas the Fas-positive cells were prone to apoptosis. In addition, EM CD8⁺ T cells in the SF were less cytotoxic, as they expressed less perforin and granzyme B. In particular, the proportions of synovial fluid mononuclear cells that were CCR4+CD8⁺ Tcells and IL-4-producing CD8⁺ T cells (i.e., Tc2 cells) were significantly higher than those in peripheral blood mononuclear cells of patients with RA and healthy controls. In addition, the number of IL-10-producing CD8⁺ suppressor T (Ts) cells increased significantly in the SF of RA patients. Especially, CD8⁺ T cells were inversely correlated with disease activity. These findings strongly suggest that EM CD8⁺ T cells in the SF are increased, likely because of inflammation, and they may be involved in modulating inflammation, thereby affecting the development and progression of RA.