PRISTANE-INDUCED ARTHRITIS IN MICE - V - SUSCEPTIBILITY TO PRISTANE-INDUCED ARTHRITIS IS DETERMINED BY THE GENETIC-REGULATION OF THE T-CELLREPERTOIRE

Objective. Pristane-induced arthritis (PIA) is an experimental seropos itive 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 maj or histocompatibility complex (MHC) and the Mls-1 loci to determine wh ether the selection of the T cells that infiltrate arthritic joints is a critical factor in disease susceptibility. Methods. Genetic regulat ion of PIA was investigated using F-1 hybrid and congenic strain analy sis to determine the influence of MHC and Mls-1 genes. The T cell rece ptor V-beta phenotypes of lymph node cells and T cells infiltrating ar thritic joints were examined with 2-color flow cytometry and reverse t ranscription-polymerase chain reaction techniques. Results, F-1 hybrid offspring from 2 major PIA-susceptible strains (DBA/1 x BALB/c) were resistant to the induction of arthritis because of the interaction bet ween genes of the MHC and the Mls-1 loci, which modified the T cell re pertoire, This conclusion was supported by the observed resistance to PIA in BALB/ c-Mls-1(a) mice, where T cells expressing the V(beta)8.1 and V(beta)6 phenotypes were absent. The receptor phenotype of T cells infiltrating arthritic joints in DBA/1 mice was markedly skewed towar d V(beta)8.1 and V(beta)6 compared with the population observed in lym ph nodes from either PIA or normal control DBA/1 mice. Conclusion. The data support the hypothesis that PIA is a T cell-mediated disease. Wh ile pristane causes a polyclonal T cell expansion that gives rise to l ymphadenopathy, the development of arthritis in susceptible strains of mice occurs due to the preservation of specific T cell subsets with t he capacity to infiltrate synovial joints.