IL-12 PROMOTES CELLULAR BUT NOT HUMORAL TYPE-II COLLAGEN-SPECIFIC T(H)1-TYPE RESPONSES IN C57BL 6 AND B10.Q MICE AND FAILS TO INDUCE ARTHRITIS/

DBA/1 (H-2(q)) and C57BL/6 (H-2(b)) mice develop an intermediate immun e response when immunized with chicken type II collagen (CII) emulsifi ed with incomplete Freund's adjuvant (IFA), Only a few animals develop a mild form of arthritis, As reported before and confirmed herein, ad ministration of IL-12 to DBA/1 mice immunized with CII in IFA strongly enhances the cellular and humoral (auto)immune response to CII and in duces severe destructive joint disease with an incidence of 80-100%, I n contrast, the same treatment did not promote joint disease in C57BL/ 6 mice, Characterization of the IL-12 effect on the CII-specific immun e response of C57BL/6 mice revealed that IL-12 promoted the developmen t of CII-specific T cells producing IFN-gamma in DBA/1 and C57BL/6 mic e equally well, However, whereas treatment with IL-12 in DBA/1 mice st rongly up-regulated the synthesis of CII-specific antibodies, especial ly of the IgG2a and IgG2b subclasses, it rather slightly down-regulate d the CII-specific IgG2a and IgG2b synthesis in C57BL/6 mice, This may indicate that the effect of IL-12 on the CII-specific antibody synthe sis is of crucial importance in the pathogenesis of type II collagen-i nduced arthritis (CIA), The failure of IL-12 to up-regulate IgG2a and IgG2b synthesis in C57BL/6 mice is specific for CII as antigen and not a general property of this strain because the keyhole limpet hemacyan in-specific antibody response is up-regulated by IL-12 in C57BL/6 mice , Furthermore, it is not the H-2(b) haplotype of C57BL/6 mice but rath er the genetic background (DBA/1 versus BL/6 or BL/10) that limits the effect of IL-12 on the CII-specific antibody response because IL-12 t reatment of CII-immunized B10.Q (H-2(q)) mice also failed to induce ar thritis and to enhance CII-specific IgG2a and IgG2b synthesis, However , as in the two other strains, injection of IL-12 promoted the develop ment of splenic T cells producing IFN-gamma upon activation with CII, These results indicate that an enhancement of the cellular and humoral anti-Cll response by IL-12 is required for inducing arthritis.