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 II 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+ alphabetaT 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-TCRVbeta and anti-TCRValpha 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-alpha receptor before transfer ameliorated arthritis development. Most importantly, we show that these T cells are MHC class II restricted, because treatment with Abs against either DQ or DR molecules ameliorates arthritis development. The MHC class II restriction was confirmed by transferring donor T cells to irradiated recipients that were syngenic, semiallogenic, or allogenic to MHC class II 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+ alphabetaT cells that are MHC class II restricted and arthritogenic.
Holmberg
Jens
J
Medical Inflammation Research, Lund University, Lund, Sweden.
Tuncel
Jonatan
J
Yamada
Hisakata
H
Lu
Shemin
S
Olofsson
Peter
P
Holmdahl
Rikard
R
D000276:Adjuvants, Immunologic / Q000633:toxicity*; D019264:Adoptive Transfer; D000818:Animals; D020296:Animals, Congenic; D001169:Arthritis, Experimental / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013729:Terpenes / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013729:Terpenes; D014409:Tumor Necrosis Factor-alpha; C009042:pristane; D007371:Interferon-gamma