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Visualization and phenotyping of proinflammatory antigen-specific T cells during collagen-induced arthritis in a mouse with a fixed collagen type II-specific transgenic T-cell receptor beta-chain
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- Merky, Patrick (author)
- Karolinska Institutet
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Batsalova, Tsvetelina (author)
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- Bockermann, Robert (author)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups
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Dzhambazov, Balik (author)
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Sehnert, Bettina (author)
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Burkhardt, Harald (author)
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- Baecklund, Johan (author)
- Karolinska Institutet
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(creator_code:org_t)
- Springer Science and Business Media LLC, 2010
- 2010
- English.
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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 12:4
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Abstract
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- Introduction: The V beta 12-transgenic mouse was previously generated to investigate the role of antigen-specific T cells in collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis. This mouse expresses a transgenic collagen type II (CII)-specific T-cell receptor (TCR) beta-chain and consequently displays an increased immunity to CII and increased susceptibility to CIA. However, while the transgenic V beta 12 chain recombines with endogenous alpha-chains, the frequency and distribution of CII-specific T cells in the V beta 12-transgenic mouse has not been determined. The aim of the present report was to establish a system enabling identification of CII-specific T cells in the V beta 12-transgenic mouse in order to determine to what extent the transgenic expression of the CII-specific beta-chain would skew the response towards the immunodominant galactosylated T-cell epitope and to use this system to monitor these cells throughout development of CIA. Methods: We have generated and thoroughly characterized a clonotypic antibody, which recognizes a TCR specific for the galactosylated CII(260-270) peptide in the V beta 12-transgenic mouse. Hereby, CII-specific T cells could be quantified and followed throughout development of CIA, and their phenotype was determined by combinatorial analysis with the early activation marker CD154 (CD40L) and production of cytokines. Results: The V beta 12-transgenic mouse expresses several related but distinct T-cell clones specific for the galactosylated CII peptide. The clonotypic antibody could specifically recognize the majority (80%) of these. Clonotypic T cells occurred at low levels in the naive mouse, but rapidly expanded to around 4% of the CD4(+) T cells, whereupon the frequency declined with developing disease. Analysis of the cytokine profile revealed an early Th1-biased response in the draining lymph nodes that would shift to also include Th17 around the onset of arthritis. Data showed that Th1 and Th17 constitute a minority among the CII-specific population, however, indicating that additional subpopulations of antigen-specific T cells regulate the development of CIA. Conclusions: The established system enables the detection and detailed phenotyping of T cells specific for the galactosylated CII peptide and constitutes a powerful tool for analysis of the importance of these cells and their effector functions throughout the different phases of arthritis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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