In:
Annals of the Rheumatic Diseases, BMJ, Vol. 77, No. 4 ( 2018-04), p. 579-588
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. 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.
Type of Medium:
Online Resource
ISSN:
0003-4967
,
1468-2060
DOI:
10.1136/annrheumdis-2017-212279
DOI:
10.1136/annrheumdis-2017-212279.supp1
DOI:
10.1136/annrheumdis-2017-212279.supp2
Language:
English
Publisher:
BMJ
Publication Date:
2018
detail.hit.zdb_id:
1481557-6