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.
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.
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.
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.