ALTERED TH1 TH2 BALANCE ASSOCIATED WITH NONMAJOR HISTOCOMPATIBILITY COMPLEX GENES IN COLLAGEN-INDUCED ARTHRITIS IN RESISTANT AND NONRESISTANT RAT STRAINS/

Collagen-induced arthritis (CIA) is a T cell-dependent disease in whic h susceptibility is controlled by genes both within and outside the ma jor histocompatibility complex (MHC). In the present study, we compare d the humoral responses and kinetics of cytokine secretion patterns in the draining lymph nodes of arthritis-susceptible DA rats and arthrit is-resistant F344 and DA MHC congenic PVG.1AV1 rats immunized with rat type II collagen (RCII) in incomplete Freund's adjuvant. The results demonstrate a marked humoral RCII response and a Th1 cytokine profile, with expression of interferon-gamma and interleukin (IL)-2 mRNA in DA rats; a limited humoral RCII response and a Th2 cytokine profile, wit h expression of IL-4 mRNA in arthritis-resistant F344 rats; and a mark ed humoral RCII response in arthritis-resistant PVG.1AV1 rats. However , in contrast to DA rats, PVG.1AV1 rats produce IgG1 autoantibodies wh ich, together with strong expression of IL-4 mRNA, indicates the invol vement of Th2 subsets. From these data, we conclude that non-MHC gene( s) determines the direction of the anti-RCII response towards a Th1 di sease-promoting, or a Th2 disease-limiting response.