Pristane, a non-antigenic adjuvant, induces MHC class II-restricted, arthritogenic T cells in the rat.

Pristane-induced arthritis (PIA) in rats, a model for rheumatoid arthritis (RA), is a T cell-dependent disease. However, pristane itself is a lipid and unable to form a stable complex with a MHC class 11 molecule. Therefore, the specificity and function of the T cells in PIA are as unclear as in rheumatoid arthritis. In this study, we show that activated CD4(+) alpha beta T cells, which target peripheral joints, transfer PIA. The pristane-primed T cells are of oligo or polyclonal origin as determined by their arthritogenicity after stimulation with several mitogenic anti-TCRV beta and anti-TCRV alpha mAbs. Arthritogenic cells secreted IFN-gamma and TNF-alpha (but not IL-4) when stimulated with Con A in vitro, and pretreatments of recipient rats with either anti-IFN-gamma or a recombinant TNF-a receptor before transfer ameliorated arthritis development. Most importantly, we show that these T cells are MHC class 11 restricted, because treatment with Abs against either DQ or DR molecules ameliorates arthritis development. The MHC class 11 restriction was confirmed by transferring donor T cells to irradiated recipients that were syngenic, semiallogenic, or allogenic to MHC class 11 molecules, in which only syngenic and semiallogenic recipients developed arthritis. These data suggest that the in vivo administration of a non-antigenic adjuvant, like pristane, activates CD4(+) alpha beta T cells that are MHC class 11 restricted and arthritogenic.