title: 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 disease pathogenesis is poorly defined. This study was undertaken to investigate the relationship between disease activity and CD8+ T cell phenotypes, production of cytokines, and production of cytotoxic molecules in the peripheral blood (PB) and synovial fluid (SF) of patients with RA.
  
  
  METHODS
  CD8+ T cell phenotypes were determined in 96 patients with RA (44 with disease in remission, 34 with active disease, 18 with low disease activity) and in 64 sex- and age-matched healthy controls. 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
  PB CD8+ T cells from RA patients with active disease exhibited an effector (CD27-CD62L-) phenotype (P = 0.005), with elevated expression of proinflammatory cytokines (tumor necrosis factor α [TNFα], interferon-γ [IFNγ], interleukin-6 [IL-6], IL-17A) when compared to healthy controls. In a state of remission, the same phenotype observed in patients with active disease persisted, including a significant increase in the frequency of CD69 (P < 0.001), but lower cytokine production was observed. SF CD8+ T cells from RA patients expressed more robust effector memory (CD27+CD62L-) and activated (CD69+) profiles compared to the T cell subsets in paired PB samples. Production of cytokines (IL-6, IL-17A, and IFNγ) by CD8+ T cells from RA PB was positively correlated within individual donors. Moreover, production of cytokines (TNFα, IFNγ, and IL-17A) by CD8+ T cells from RA PB positively correlated with the Disease Activity Score in 28 joints.
  
  
  CONCLUSIONS
  The activation status and proinflammatory potential of CD8+ T cell subsets observed in the RA patients in this study strongly suggest that a phenotype of local and systemic cytotoxic effector T cells plays a role in this disease.
authors.affiliation: University of Coimbra, Coimbra, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Carvalheiro
authors.forename: Cátia
authors.initials: C
authors.lastname: Duarte
authors.forename: Sandra
authors.initials: S
authors.lastname: Silva-Cardoso
authors.forename: José A P
authors.initials: JA
authors.lastname: da Silva
authors.forename: M Margarida
authors.initials: MM
authors.lastname: Souto-Carneiro
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000378:metabolism; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000166:cytology
chemical_list: C527276:CXCR4 protein, human; D016207:Cytokines; D019718:Receptors, CXCR4