title: Increased arthritis susceptibility in cartilage proteoglycan-specific T cell receptor-transgenic mice.
abstract: OBJECTIVE
  To better understand the role of antigen (arthritogenic epitope)-specific T cells in the development of autoimmune arthritis.
  
  
  METHODS
  A transgenic (Tg) mouse expressing the T cell receptor (TCR) Valpha1.1 and V(beta)4 chains specific for a dominant arthritogenic epitope (designated 5/4E8) of human cartilage proteoglycan (HuPG) aggrecan was generated. This TCR-Tg mouse strain was backcrossed into the PG-induced arthritis (PGIA)-susceptible BALB/c strain and tested for arthritis incidence and severity.
  
  
  RESULTS
  CD4+ TCR-Tg T cells carried functionally active TCR specific for a dominant arthritogenic epitope of HuPG (5/4E8). T cells of naive TCR-Tg mice were in an activated stage, since the in vitro response to HuPG or to peptide stimulation induced interferon-gamma and interleukin-4 production. TCR-Tg mice uniformly, without exception, developed severe and progressive polyarthritis, even without adjuvant. Inflamed joints showed extensive cartilage degradation and bone erosions, similar to that seen in the arthritic joints of wild-type BALB/c mice with PGIA. Spleen cells from both naive and HuPG-immunized arthritic TCR-Tg mice could adoptively transfer arthritis when injected into syngeneic BALB/c.SCID recipient mice.
  
  
  CONCLUSIONS
  TCR-Tg BALB/c mice display increased arthritis susceptibility and develop aggravated disease upon in vivo antigen stimulation. This model using TCR-Tg mice is a novel and valuable research tool for studying mechanisms of antigen (arthritogenic epitope)-driven regulation of arthritis and understanding how T cells recognize autoantigen in the joints. This type of mouse could also be used to develop new immunomodulatory strategies in T cell-mediated autoimmune diseases.
authors.affiliation: Utrecht University, Utrecht, The Netherlands.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Berlo
authors.forename: Teun
authors.initials: T
authors.lastname: Guichelaar
authors.forename: Corlinda B
authors.initials: CB
authors.lastname: Ten Brink
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van Kooten
authors.forename: Femke
authors.initials: F
authors.lastname: Hauet-Broeren
authors.forename: Katalin
authors.initials: K
authors.lastname: Ludanyi
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: Chris P
authors.initials: CP
authors.lastname: Broeren
authors.forename: Tibor T
authors.initials: TT
authors.lastname: Glant
mesh_terms: D019264:Adoptive Transfer; D053674:Aggrecans; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002356:Cartilage / Q000276:immunology / Q000473:pathology; D017690:Cell Transplantation; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007178:Inbreeding; D037181:Lectins, C-Type / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C508320:Acan protein, mouse; D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D018984:Epitopes, T-Lymphocyte; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell