CD8+T cell profiles in patients with rheumatoid arthritis and their relationship to disease activity

Abstract

Objective

CD8+T cells are abundant in rheumatoid arthritis (RA). However, their role in the disease pathogenesis is poorly defined. Here we investigated the relationship between disease activity and CD8+T cell phenotypes, production of cytokines and cytotoxic molecules in RA peripheral blood (PB) and synovial fluid (SF).

Methods

CD8+T cell phenotypes were determined in 96 patients with RA (44 in remission, 34 with active disease) and in 64 gender and age-matched healthy controls (HC). Ten paired PB and SF samples from patients with active RA were analyzed. The expression of surface markers, cytokines and proteolytic enzymes in CD8+T cells was evaluated using flow-cytometry.

Results

The PB CD8+T cells from RA patients with active disease exhibited an effector CD27-CD62L- (p=0.005) phenotype with elevated proinflammatory cytokine expression (TNF-α, IFN-γ, IL-6, IL-17A) when compared to HC. The phenotype observed in patients with active disease persisted in remission, with a significant increase in the frequency of CD69 (p<0.001) and was associated with lower cytokine production. CD8+T cells from SF expressed more robust effector memory (CD27+CD62L-) and activated (CD69+) profiles compared with paired blood-derived subsets. Cytokine-production (IL-6, IL-17A, and IFN-γ) by CD8+T cells from PB and SF was positively correlated within individual donors. The production of cytokines (TNF-α, IFN-γ, IL-17A) by CD8+T cells in the PB from RA patients positively correlated with DAS28.

Conclusion

Herein we characterize the activation status and proinflammatory potential of CD8+T cells subsets in RA patients. This activation status strongly suggests a local and systemic effector cytotoxic role in the disease.