Prendergast, C. T., Patakas, A., Al-Khabouri, S., McIntyre, C. L., McInnes, I. B. , Brewer, J. M. , Garside, P. and Benson, R. A. (2018) Visualising the interaction of CD4 T cells and DCs in the evolution of inflammatory arthritis. Annals of the Rheumatic Diseases, 77(4), pp. 579-588. (doi: 10.1136/annrheumdis-2017-212279) (PMID:29358281)
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Abstract
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. 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. 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. 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.
Item Type: | Articles |
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Keywords: | T cells, autoimmune diseases, early rheumatoid arthritis, rheumatoid arthritis. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McInnes, Professor Iain and Prendergast, Dr Catriona and Garside, Professor Paul and Brewer, Professor James and Patakas, Dr Agapitos and Benson, Dr Robert and McIntyre, Claire and Al Khabouri, Shaima Mazin Jawad |
Authors: | Prendergast, C. T., Patakas, A., Al-Khabouri, S., McIntyre, C. L., McInnes, I. B., Brewer, J. M., Garside, P., and Benson, R. A. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Annals of the Rheumatic Diseases |
Publisher: | BMJ Publishing Group |
ISSN: | 0003-4967 |
ISSN (Online): | 1468-2060 |
Published Online: | 22 January 2018 |
Copyright Holders: | Copyright © 2018 The Authors |
First Published: | First published in Annals of the Rheumatic Diseases 77(4): 579-588 |
Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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