IL-12 promotes cellular but not humoral type II collagen-specific Th1-type responses in C57BL/6 and B10.Q mice and fails to induce arthritis

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Abstract
DBA/1 (H-2q) and C57BL/6 (H-2b) mice develop an Intermediate immune response when immunized with chicken type II collagen (Cll) emulsified with Incomplete Freund's adjuvant (IFA). Only a few animals develop a mild form of arthritis. As reported before and confirmed herein, administration of IL-12 to DBA/1 mice immunized with Cll in IFA strongly enhances the cellular and humoral (auto)immune response to Cll and Induces severe destructive joint disease with an incidence of 80–100%. In contrast, the same treatment did not promote joint disease In C57BL/6 mice. Characterization of the IL-12 effect on the Cll-specific immune response of C57BL/6 mice revealed that IL-12 promoted the development of Cll-specific T cells producing IFN-γ in DBA/1 and C57BL/6 mice equally well. However, whereas treatment with IL-12 In DBA/1 mice strongly up-regulated the synthesis of Cll-specific antibodies, especially of the lgG2a and lgG2b subclasses, it rather slightly down-regulated the Cll-specific lgG2a and lgG2b synthesis in C57BL/6 mice. This may indicate that the effect of IL-12 on the Cll-speclfic antibody synthesis is of crucial Importance In the pathogenesis of type II collagen-induced arthritis (CIA). The failure of IL-12 to up-regulate lgG2a and lgG2b synthesis in C57BL/6 mice is specific for Cll as antigen and not a general property of this strain because the keyhole limpet hemacyanin-specific antibody response is up-regulated by IL-12 In C57BL/6 mice. Furthermore, it is not the H-2b haplotype of C57BL/6 mice but rather the genetic background (DBA/1 versus BL/6 or BL/10) that limits the effect of IL-12 on the Cll-speclfic antibody response because IL-12 treatment of CIl-immunlzed B10.Q (H-2q) mice also failed to induce arthritis and to enhance Cll-specific lgG2a and lgG2b synthesis. However, as In the two other strains, Injection of IL-12 promoted the development of splenic T cells producing IFN-γ upon activation with Cll. These results Indicate that an enhancement of the cellular and humoral anti-CII response by IL-12 is required for inducing arthritis.

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