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Characterisation of CD8+ T cell subsets in the synovial fluid and peripheral blood of rheumatoid arthritis patients
  1. H Carvalheiro1,
  2. D Antunes1,
  3. C Duarte2,
  4. S Silva-Cardoso1,
  5. T Rodrigues-Sousa1,
  6. JA da Silva2,3,
  7. MM Souto-Carneiro1,3
  1. 1Immunology Group, Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
  2. 2Rheumatology Department, Hospitais da Universidade de Coimbra, Coimbra, Portugal
  3. 3Immunology Department, Faculty of Medicine, Coimbra, Portugal; HC and DA contributed equally to this work


Background and objectives Detailed information on CD8+ T cells in rheumatoid arthritis (RA) is still reduced. However, studies on animal models of arthritis from the authors' team and others suggest a major potential role of CD8+ T cells in the pathogenesis of chronic polyarthritis.

In the present study the authors characterised the phenotype and cytokine-production profile of CD8+ T cells from peripheral blood (PB) and synovial fluid (SF) of RA patients.

Materials and methods Unstimulated CD8+ T cells from the PB and SF of 40 patients with established RA were analysed by flow-cytometry for cell surface markers expression and intracellular cytokine production, and compared to the ones present in the PB of 15 healthy donors.

Results 40% of the total T cells infiltrating the SF were CD8+. The SF was characterised by a significant (p<0.05) accumulation of mature CD45Ro+CD8+ T cells when compared to the RA and control PB. The majority of these CD8+ T cells infiltrating the SF presented an effector phenotype (CD62LCD27 short-term effector, or CD62LCD27+ central effector), and the presence of the activation markers CD69 and CD25 were significantly (p<0.05) higher in the SF than in the PB of RA patients or controls. The expression of the pro-inflammatory homing chemokine receptors CCR7 and CXCR4 were significantly (p<0.05) increased in the short-term effector CD62LCD27CD8+ T cells and in the SF central memory CD62L+CD27+CD8+ T cells when compared to RA PB. The intracellular expression of the pro-inflammatory cytokines IFN-γ, interleukin-6, interleukin-17 and tumour necrosis factor-α in central memory CD62L+CD8+ T cells were significantly (p<0.05) higher in the SF when compared to RA PB, and absent in controls.

Conclusions The present study presents strong evidence for a marked role of CD8+ T cells in RA pathogenesis. The authors propose that activated effector CD8+ T cells, home into the SF, where they might contribute to articular destruction and maintenance of a chronic pro-inflammatory environment through the production of cytokines and cytotoxic agents.

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