title: Pristane-induced arthritis in mice. V. Susceptibility to pristane-induced arthritis is determined by the genetic regulation of the T cell repertoire.
abstract: OBJECTIVE
  Pristane-induced arthritis (PIA) is an experimental seropositive arthritis that is characterized by serologic and cellular immune abnormalities and is dependent on the presence of a competent CD4+ T cell population. We examined the regulation of PIA by genes of the major histocompatibility complex (MHC) and the Mls-1 loci to determine whether the selection of the T cells that infiltrate arthritic joints is a critical factor in disease susceptibility.
  
  
  METHODS
  Genetic regulation of PIA was investigated using F1 hybrid and congenic strain analysis to determine the influence of MHC and Mls-1 genes. The T cell receptor Vbeta phenotypes of lymph node cells and T cells infiltrating arthritic joints were examined with 2-color flow cytometry and reverse transcription-polymerase chain reaction techniques.
  
  
  RESULTS
  F1 hybrid offspring from 2 major PIA-susceptible strains (DBA/1 x BALB/c) were resistant to the induction of arthritis because of the interaction between genes of the MHC and the Mls-1 loci, which modified the T cell repertoire. This conclusion was supported by the observed resistance to PIA in BALB/ c-Mls-1a mice, where T cells expressing the Vbeta8.1 and Vbeta6 phenotypes were absent. The receptor phenotype of T cells infiltrating arthritic joints in DBA/1 mice was markedly skewed toward Vbeta8.1 and Vbeta6 compared with the population observed in lymph nodes from either PIA or normal control DBA/1 mice.
  
  
  CONCLUSIONS
  The data support the hypothesis that PIA is a T cell-mediated disease. While pristane causes a polyclonal T cell expansion that gives rise to lymphadenopathy, the development of arthritis in susceptible strains of mice occurs due to the preservation of specific T cell subsets with the capacity to infiltrate synovial joints.
authors.affiliation: Wayne State University Medical School, Detroit, Michigan, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Wooley
authors.forename: S
authors.initials: S
authors.lastname: Sud
authors.forename: J D
authors.initials: JD
authors.lastname: Whalen
authors.forename: S
authors.initials: S
authors.lastname: Nasser
mesh_terms: D000483:Alleles; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology*; D017252:CD3 Complex / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics / Q000276:immunology; D006824:Hybridization, Genetic; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007166:Immunosuppressive Agents; D015994:Incidence; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013729:Terpenes
chemical_list: D017252:CD3 Complex; D007135:Immunoglobulin Variable Region; D007166:Immunosuppressive Agents; D013729:Terpenes; C009042:pristane