REDUCED SUSCEPTIBILITY TO COLLAGEN-INDUCED ARTHRITIS IN MICE DEFICIENT IN IFN-GAMMA RECEPTOR

Collagen-induced arthritis (CU) is an arthritic model that was develop ed after immunization with type II collagen (CII), Apparently, contrad ictory results have been reported regarding the role of IFN-gamma in t he development of CW, Therefore, we employed IFN-gamma R-deficient mic e to study the role of IFN-gamma. To introduce the CW susceptibility g ene (H-2(q)), IFN-gamma R-deficient (H-2(b/b)/IFN-gamma R-/-) mice wer e mated with DBA/1 (H-2(q/q)/IFN-gamma R+/+) mice; next, the F-1 mice were interbred to yield F-2 offspring bearing different combinations o f H-2 (H-2(q/q), H-2(q/b), and H-2(b/b)) and IFN-gamma R (IFN-gamma R/+, IFN-gamma R+/-, and IFN-gamma R-/-) genes. Although the H-2(q) all ele appeared to confer susceptibility to CW, mice that were homozygous for the IFN-gamma R mutation shelved a substantially decreased incide nce and severity of CW. The CII-specific IgG levels of serum samples, which are known to be involved in the development of CU, were remarkab ly reduced in IFN-gamma R-/- mice. Furthermore, the anti CII IgG2a lev els controlled by IFN-gamma R were significantly reduced in IFN-gamma R-/- F-2 mice compared with those seen in IFN-gamma R+/+ and IFN-gamma R+/- mice, although the levels of all IgG subclass Abs examined were lower in IFN-gamma R-/- mice than in IFN-gamma R+/+ mice. No clear evi dence of the imbalance of Th1/Th2 cytokines was observed in CII-immuni zed, IFN-gamma R-deficient mice, Taken together, these results suggest that IFN-gamma exacerbates CW by affecting, at least, levels of CII-s pecific Ige Ab rather than the imbalance of Th1/Th2 cells.