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Visualising the interaction of CD4 T cells and DCs in the evolution of inflammatory arthritis
  1. Catriona T Prendergast,
  2. Agapitos Patakas,
  3. Shaima Al-Khabouri,
  4. Claire L McIntyre,
  5. Iain B McInnes,
  6. James M Brewer,
  7. Paul Garside,
  8. Robert A Benson
  1. Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
  1. Correspondence to Dr Robert A Benson, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK; robert.benson{at}


Objectives Successful early intervention in rheumatoid arthritis (RA) with the aim of resetting immunological tolerance requires a clearer understanding of how specificity, cellular kinetics and spatial behaviour shape the evolution of articular T cell responses. We aimed to define initial seeding of articular CD4+ T cell responses in early experimental arthritis, evaluating their dynamic behaviour and interactions with dendritic cells (DCs) in the inflamed articular environment.

Methods Antigen-induced arthritis was used to model articular inflammation. Flow cytometry and PCR of T cell receptor (TCR) diversity genes allowed phenotypic analysis of infiltrating T cells. The dynamic interactions of T cells with joint residing DCs were visualised using intravital multiphoton microscopy.

Results Initial recruitment of antigen-specific T cells into the joint was paralleled by accumulation of CD4+ T cells with diverse antigen-receptor expression and ability to produce tumour necrosis factor alpha (TNFα) and interferon gamma (IFNγ) on mitogenic restimulation. A proportion of this infiltrate demonstrated slower motility speeds and engaged for longer periods with articular DCs in vivo. Abatacept treatment did not disrupt these interactions but did reduce T cell expression of inducible costimulatory (ICOS) molecule. We also demonstrated that non-specific CD4+ T cells could be recruited during these early articular events.

Conclusions We demonstrate that CD4+ T cells engage with articular DCs supporting antigen specific T cell reactivation. This cellular dialogue can be targeted therapeutically to reduce local T cell activation.

  • autoimmune diseases
  • early rheumatoid arthritis
  • rheumatoid arthritis
  • T cells

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  • Handling editor Tore K Kvien

  • Contributors CTP and RAB: designed the research, performed the experiments, constructed the figures, analysed the data and wrote the manuscript; RAB: performed the imaging studies; SA and CLM: provided technical assistance and helped with design of TCR Vβ repertoire analysis; AP: provided technical assistance and helped in design of abatacept experiments; and IBM, JMB and PG: designed the research and contributed to writing the paper.

  • Funding This work was supported by Arthritis Research UK (ARUK) programme grant number 19788 and the IMI-supported programme BTCure. CTP, SA, CLM, IBM, JMB, PG and RAB are members of the ARUK Pathogenesis Centre of Excellence (RACE), which is part-funded by Arthritis Research UK through grant number 20298. The Centre is a collaborative network between the Universities of Glasgow, Newcastle and Birmingham. We would also like to acknowledge the assistance of the Institute of Infection, Immunity and Inflammation Flow Cytometry Facility at the University of Glasgow.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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