Background and Objectives CD8+T cells are known to be present in the synovial fluid and synovium of rheumatoid arthritis. However, their role in the disease pathogenesis remains largely unexplored. This work intended to characterise blood and synovial fluid CD8+T cell functional subsets found in patients with rheumatoid arthritis and explore their importance in regulating the activity of the disease.
Methods The functional phenotypes of CD8+T cells were determined in seventy-eight patients with rheumatoid arthritis (forty-four in remission (DAS28 < 2.6), thirty-four with active disease (DAS28 > 3.2)) and the results were compared to those of sixty-four sex and age-matched healthy controls (HC). Ten paired samples of blood and synovial fluid (SF) from patients with active disease were also analysed, and the expression of surface markers, cytokines and proteolytic enzymes of CD8+T cells were determined.
Results Data shows that peripheral blood CD8+T cells from both patients with active disease and in remission present an activated phenotype with a marked pro-inflammatory profile. Remission is associated with a lower production of proinflammatory mediators, such as IL-6 and IFNγ, but the changes in cell subsets observed in active disease persist or are even accentuated, with the frequency of the central memory CD27+CD62L+CCR7+CD8+T cells significantly reduced, and the short-term effector CD27-CD62L-CD8+and the activated subset CD69+CD8+ T cell subsets significantly increased when compared to healthy controls. The CD8+T cells present in the SF of active RA present a more exacerbated effector memory (CD27+CD62L-) and activated (CD25+and CD69+) CD8+T cell phenotype than the ones in the paired blood samples. Finally, we report that the production of cytokines by CD8+T cells from the synovial fluid is correlated with that observed in peripheral blood samples, with increased production of proinflammatory cytokines such as IL-6 and TNFα.
Conclusions Our data demonstrate major shifts in CD8+T cells subsets and in their cytokine production in rheumatoid arthritis, which are related to disease activity. This suggests that these cells play relevant roles in the pathogenesis of the disease.