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

• Autor(a) principal: Carvalheiro, Helena
• Data de Publicação: 2014
• Outros Autores: Duarte, Cátia, Silva-Cardoso, Sandra, Silva, José A. P. da, Souto-Carneiro, M. Margarida
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/27565; https://doi.org/10.1002/art.38941
• topic: CD8+T cells in RA

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.