Visualising the interaction of CD4 T cells and DCs in the evolution of inflammatory arthritis
| Autor: | James M. Brewer, Robert A. Benson, Catriona T. Prendergast, Iain B. McInnes, Shaima Al-Khabouri, Agapitos Patakas, Paul Garside, Claire L. McIntyre |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases CD4-Positive T-Lymphocytes T cell Inflammatory arthritis Immunology Receptors Antigen T-Cell Arthritis Mice Transgenic Lymphocyte Activation General Biochemistry Genetics and Molecular Biology Flow cytometry Abatacept 03 medical and health sciences Interferon-gamma Mice 0302 clinical medicine Rheumatology Immune Tolerance Immunology and Allergy Medicine Animals Interferon gamma Immunity Cellular medicine.diagnostic_test business.industry Tumor Necrosis Factor-alpha T-cell receptor Dendritic Cells medicine.disease Arthritis Experimental Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Tumor necrosis factor alpha business 030215 immunology medicine.drug |
| Zdroj: | Annals of the rheumatic diseases. 77(4) |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | ObjectivesSuccessful 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.MethodsAntigen-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.ResultsInitial 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.ConclusionsWe 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. |
| Databáze: | OpenAIRE |
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