Kageyama Y, Koide Y, Yoshida A, Uchijima M, Arai T, Miyamoto S, Ozeki T, Hiyoshi M, Kushida K, Inoue T
Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Japan.
J Immunol. 1998 Aug 1;161(3):1542-8.
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-gamma in the development of CIA. Therefore, we employed IFN-gamma R-deficient mice to study the role of IFN-gamma. To introduce the CIA susceptibility gene (H-2q), IFN-gamma R-deficient (H-2b/b/IFN-gamma R-/-) mice were mated with DBA/1 (H-2q/q/IFN-gamma R+/+) 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-gamma R (IFN-gamma R+/+, IFN-gamma R+/-, and IFN-gamma R-/-) genes. Although the H-2q allele appeared to confer susceptibility to CIA, mice that were homozygous for the IFN-gamma 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-gamma R-/- mice. Furthermore, the anti-CII IgG2a levels controlled by IFN-gamma R were significantly reduced in IFN-gamma R-/- F2 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 evidence of the imbalance of Th1/Th2 cytokines was observed in CII-immunized, IFN-gamma R-deficient mice. Taken together, these results suggest that IFN-gamma exacerbates CIA by affecting, at least, levels of CII-specific IgG Ab rather than the imbalance of Th1/Th2 cells.
胶原诱导性关节炎（CIA）是一种在用II型胶原（CII）免疫后建立的关节炎模型。显然，关于IFN-γ在CIA发病过程中的作用，已有相互矛盾的报道。因此，我们使用IFN-γ受体缺陷小鼠来研究IFN-γ的作用。为了引入CIA易感性基因（H-2q），将IFN-γ受体缺陷（H-2b/b/IFN-γR-/-）小鼠与DBA/1（H-2q/q/IFN-γR+/+）小鼠交配；接下来，将F1小鼠进行杂交，以产生携带不同H-2（H-2q/q、H-2q/b和H-2b/b）和IFN-γ受体（IFN-γR+/+、IFN-γR+/-和IFN-γR-/-）基因组合的F2后代。尽管H-2q等位基因似乎赋予了对CIA的易感性，但IFN-γ受体突变纯合子小鼠的CIA发病率和严重程度显著降低。已知参与CIA发病的血清样本中CII特异性IgG水平在IFN-γR-/-小鼠中显著降低。此外，与IFN-γR+/+和IFN-γR+/-小鼠相比，IFN-γR-/- F2小鼠中受IFN-γ受体控制的抗CII IgG2a水平显著降低，尽管在IFN-γR-/-小鼠中检测的所有IgG亚类抗体水平均低于IFN-γR+/+小鼠。在CII免疫的IFN-γ受体缺陷小鼠中未观察到Th1/Th2细胞因子失衡的明确证据。综上所述，这些结果表明，IFN-γ至少通过影响CII特异性IgG抗体水平而非Th1/Th2细胞失衡来加重CIA。
