Advanced

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

Merky, Patrick; Batsalova, Tsvetelina; Bockermann, Robert LU ; Dzhambazov, Balik; Sehnert, Bettina; Burkhardt, Harald and Baecklund, Johan (2010) In Arthritis Research and Therapy 12(4).
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis Research and Therapy
volume
12
issue
4
publisher
BioMed Central
external identifiers
  • wos:000283841500029
  • scopus:77955098679
ISSN
1478-6362
DOI
10.1186/ar3108
language
English
LU publication?
yes
id
6e5b7cef-2ba9-4356-b61b-0f8b34c58676 (old id 1753465)
date added to LUP
2011-01-04 08:13:36
date last changed
2018-05-29 11:39:39
@article{6e5b7cef-2ba9-4356-b61b-0f8b34c58676,
  abstract     = {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.},
  author       = {Merky, Patrick and Batsalova, Tsvetelina and Bockermann, Robert and Dzhambazov, Balik and Sehnert, Bettina and Burkhardt, Harald and Baecklund, Johan},
  issn         = {1478-6362},
  language     = {eng},
  number       = {4},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {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},
  url          = {http://dx.doi.org/10.1186/ar3108},
  volume       = {12},
  year         = {2010},
}