IL-12 promotes cellular but not humoral type II collagen-specific Th 1-type responses in C57BL/6 and B10.Q mice and fails to induce arthritis.
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.
Szeliga
J
J
Institut für Immunologie, Mainz, Germany.
Hess
H
H
Rüde
E
E
Schmitt
E
E
Germann
T
T
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage; D001168:Arthritis / Q000209:etiology* / Q000276:immunology; D002645:Chickens; D003094:Collagen / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D007111:Immunity, Cellular; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018417:Th1 Cells / Q000276:immunology*
D000941:Antigens; D007074:Immunoglobulin G; D018664:Interleukin-12; D003094:Collagen; D005620:Freund's Adjuvant; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin