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

Collagen-induced arthritis (CIA) is an arthritic model that was developed after immunization with type II collagen (CII). Ap-parently, contradictory results have been reported regarding the role of IFN- g in the development of CIA. Therefore, we employed IFN- g R-deficient mice to study the role of IFN- g . To introduce the CIA susceptibility gene (H-2 q ), IFN- g R-deficient (H-2 b/b /IFN- g R 2 / 2 ) mice were mated with DBA/1 (H-2 q/q /IFN- g R 1 / 1 ) mice; next, the F 1 mice were interbred to yield F 2 offspring bearing different combinations of H-2 (H-2 q/q , H-2 q/b , and H-2 b/b ) and IFN- g R (IFN- g R 1 / 1 , IFN- g R 1 / 2 , and IFN- g R 2 / 2 ) genes. Although the H-2 q allele appeared to confer susceptibility to CIA, mice that were homozygous for the IFN- g R 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- g R 2 / 2 mice. Furthermore, the anti-CII IgG2a levels controlled by IFN- g R were significantly reduced in IFN- g R 2 / 2 F 2 mice compared with those seen in IFN- g R 1 / 1 and IFN- g R 1 / 2 mice, although the levels of all IgG subclass Abs examined were lower in IFN- g R 2 / 2 mice than in IFN- g R 1 / 1 mice. No clear evidence of the imbalance of Th1/Th2 cytokines was observed in CII-immunized, IFN- g R-deficient mice. Taken together, these results suggest that IFN- g exacerbates CIA by affecting, at least, levels of CII-specific IgG Ab rather than the imbalance of Th1/Th2 cells. The Journal of Immunology, 1998, 161: 1542–1548.