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 F, hybrid and congenic strain analysis to determine the influence of MHC and Mls-1 genes. The T cell receptor V, phenotypes of lymph node cells and T cells infiltrating arthritic joints were examined with 2-color flow cytometry and reverse transcriptionpolymerase chain reaction techniques.Results. F, hybrid offspring from 2 major PIAsusceptible strains (DBN1 x BALBlc) were resistant to the induction of arthritis because of the interaction between genes of the MHC and the Mls-I loci, which modified the T cell repertoire. This conclusion was supported by the observed resistance to PIA in BALB/ c-Mls-I" mice, where T cells expressing the V,8.1 and V,6 phenotypes were absent. The receptor phenotype of T cells infiltrating arthritic joints in DBN1 mice was markedly skewed toward V,8.

The Human Endoplasmic Reticulum Molecular Chaperone BiP Is an Autoantigen for Rheumatoid Arthritis and Prevents the Induction of Experimental Arthritis

“…CIA and PIA were induced in DBA/1 mice according to previously described protocols (25,26). Mice were bled before induction of arthritis (15 animals), at the onset of CIA (16 animals), and at the onset of PIA (14 animals).…”

“…Arthritis was scored 8 wk later. Where indicated, arthritis was scored as the number of animals and the number of joints per animal with clinical arthritis and the histological appearance of the joints as previously described (25,26,28,29). Modulation of adjuvant arthritis with BiP.…”

Animal models of rheumatoid arthritis and related inflammation

“…CD4+ Th2 cells, specific for mycobacterial 65-kD heat shock protein, protect against PIA [60] In contrast to CIA, to which BALB/c mice are resistant, both DBA/1 and BALB/c are susceptible to PIA. However, F1 hybrid offspring from DBA/1 x BALB/c mice are resistant to the induction of arthritis because of the interaction between H-2E class II molecules of BALB/c mice and the Mls-1 a loci (Mtv-7 on chromosome 1) of DBA/1 mice, which modifies the T cell repertoire [61]. Congenic BALB/c-MLs-1␣ mice, in which T cells expressing the V b 8.1 and V b 6 are absent, are resistant to PIA [61], suggesting that although, pristane causes polyclonal T-cell expansion that gives rise to lymphoadenopathy, the development of arthritis in susceptible strains of mice is mediated by specific T-cell subsets with the capacity to infiltrate the articular synovium.…”

Pristane-induced lupus as a model of human lupus arthritis: evolvement of autoantibodies, internal organ and joint inflammation

“…15,[22][23][24][25][26][27] In early reports on pristane-induced arthritis the systemic, lupus-like nature of pristane-induced autoimmune disease has not been characterized and PIL arthritis has been considered typical for osteoarthritis or, more often, for RA: [26][27][28][29] BALB/c, DBA-1 and CBA strains have been considered susceptible, while (based on clinical observations) C57BL/6 have not. 15,26,30 Since BALB/c and especially C57BL/6 mice often serve as background for genetically altered mouse models (whose use might allow the development of valuable insights into lupus pathogenesis), we herein investigated BALB/c and C57BL/6 mice for the occurrence and detailed clinical and histopathological presentation of arthritis.…”