Szeliga J, Hess H, Rüde E, Schmitt E, Germann T
Institut für Immunologie, Mainz, Germany.
Int Immunol. 1996 Aug;8(8):1221-7. doi: 10.1093/intimm/8.8.1221.
DBA/1 (H-2q) and C57BL/6 (H-2b) mice develop an intermediate immune responses when immunized with chicken type II collagen (CII) 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 CII in IFA strongly enhances the cellular and humoral (auto)immune response to CII 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 CII-specific immune response of C57BL/6 mice revealed that IL-12 promoted the development of CII-specific T cells producing IFN-gamma 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 CII-specific antibodies, especially of the IgG2a and IgG2b subclasses, it rather slightly down-regulated 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 synthesis is of crucial importance in the pathogenesis of type II collagen-induced 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 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 CII-specific antibody response because IL-12 treatment of CII-immunized B10.Q (H-2q) mice also failed to induce arthritis and to enhance CII-specific IgG2a and IgG2b synthesis. However, as in the two other strains, injection of IL-12 promoted the development of splenic T cells producing IFN-gamma upon activation with CII. These results indicate that an enhancement of the cellular and humoral anti-CII response by IL-12 is required for inducing arthritis.
用不完全弗氏佐剂（IFA）乳化的鸡II型胶原（CII）免疫DBA/1（H-2q）和C57BL/6（H-2b）小鼠时，它们会产生中等程度的免疫反应。只有少数动物会出现轻度关节炎。如先前报道并在此得到证实，给用IFA中CII免疫的DBA/1小鼠注射IL-12会强烈增强对CII的细胞和体液（自身）免疫反应，并诱导严重的破坏性关节疾病，发病率为80-100%。相比之下，相同处理在C57BL/6小鼠中并未促进关节疾病。对IL-12对C57BL/6小鼠CII特异性免疫反应的影响进行表征发现，IL-12在DBA/1和C57BL/6小鼠中同样能很好地促进产生IFN-γ的CII特异性T细胞的发育。然而，虽然在DBA/1小鼠中用IL-12处理会强烈上调CII特异性抗体的合成，尤其是IgG2a和IgG2b亚类，但在C57BL/6小鼠中它却略微下调了CII特异性IgG2a和IgG2b的合成。这可能表明IL-12对CII特异性抗体合成的影响在II型胶原诱导的关节炎（CIA）发病机制中至关重要。IL-12未能上调C57BL/6小鼠中IgG2a和IgG2b的合成是CII作为抗原所特有的，而不是该品系的一般特性，因为在C57BL/6小鼠中，IL-12会上调血蓝蛋白特异性抗体反应。此外，限制IL-12对CII特异性抗体反应影响的不是C57BL/6小鼠的H-2b单倍型，而是遗传背景（DBA/1与BL/6或BL/10），因为用IL-12处理用CII免疫的B10.Q（H-2q）小鼠也未能诱导关节炎和增强CII特异性IgG2a和IgG2b的合成。然而，与其他两个品系一样，注射IL-12会促进脾T细胞在被CII激活后产生IFN-γ。这些结果表明，IL-12增强细胞和体液抗CII反应是诱导关节炎所必需的。
