Visualising the interaction of CD4 T cells and DCs in the evolution of inflammatory arthritis

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
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 Al Khabouri, Shaima Mazin Jawad and Patakas, Dr Agapitos and Benson, Dr Robert and McIntyre, Claire
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 > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
568541Defining the Role of Cell Migration in the Initiation and Regulation of Pathogenesis in Inflammatory ArthritisPaul GarsideArthritis Research UK (ARTRESUK)19788III -IMMUNOLOGY
602451Rheumatoid Arthritis Centre of Excellence (RACE - Towards a Cure)Iain McInnesArthritis Research UK (ARTRESUK)MP20298III -IMMUNOLOGY