Reduced Susceptibility to Collagen-Induced Arthritis in Mice Deficient in IFN-γ Receptor

Collagen-induced arthritis (CIA) is an arthritic model that was developed after immunization with type II collagen (CII). Apparently, contradictory results have been reported regarding the role of IFN-γ in the development of CIA. Therefore, we employed IFN-γR-deficient mice to study the role of IFN-γ. To introduce the CIA susceptibility gene (H-2q), IFN-γR-deficient (H-2b/b/IFN-γR−/−) mice were mated with DBA/1 (H-2q/q/IFN-γR+/+) mice; next, the F1 mice were interbred to yield F2 offspring bearing different combinations of H-2 (H-2q/q, H-2q/b, and H-2b/b) and IFN-γR (IFN-γR+/+, IFN-γR+/−, and IFN-γR−/−) genes. Although the H-2q allele appeared to confer susceptibility to CIA, mice that were homozygous for the IFN-γR mutation showed a substantially decreased incidence and severity of CIA. The CII-specific IgG levels of serum samples, which are known to be involved in the development of CIA, were remarkably reduced in IFN-γR−/− mice. Furthermore, the anti-CII IgG2a levels controlled by IFN-γR were significantly reduced in IFN-γR−/− F2 mice compared with those seen in IFN-γR+/+ and IFN-γR+/− mice, although the levels of all IgG subclass Abs examined were lower in IFN-γR−/− mice than in IFN-γR+/+ mice. No clear evidence of the imbalance of Th1/Th2 cytokines was observed in CII-immunized, IFN-γR-deficient mice. Taken together, these results suggest that IFN-γ exacerbates CIA by affecting, at least, levels of CII-specific IgG Ab rather than the imbalance of Th1/Th2 cells.