Matsumoto T, Ametani A, Hachimura S, Iwaya A, Taguchi Y, Fujita K, Shigehisa T, Kaminogawa S
Department of Applied Biological Chemistry, The University of Tokyo, Tokyo, 113-8657, Japan.
Clin Immunol Immunopathol. 1998 Jul;88(1):70-9. doi: 10.1006/clin.1998.4521.
Collagen-induced arthritis (CIA) is an autoimmune animal model for some types of human rheumatoid arthritis (RA). We have evaluated the effectiveness of intranasal administration of antigen in inhibiting CIA in DBA/1 mice. The intranasal administration of heat-denatured or trypsin-digested bovine type II collagen (CII) before immunization with CII strongly delayed the onset of CIA, whereas administration of native CII did not do so. The mice administered denatured or digested CII possessed much lower titers of anti-CII IgG2a than the control mice, whereas titers of anti-CII IgG1 and IgG2b were unchanged or slightly decreased. Responding to CII and peptides containing immunodominant T cell determinants, lymph node cells from mice administered denatured CII produced less IFN-gamma. These results suggest that intranasal administration of antigen downregulated preferentially Th1-type responses, whereas an enhanced Th2-type response was not observed. We demonstrate that the methods shown here are a possible treatment for rheumatoid arthritis.
胶原诱导的关节炎（CIA）是某些类型人类类风湿关节炎（RA）的一种自身免疫动物模型。我们评估了鼻内给予抗原对抑制DBA/1小鼠CIA的有效性。在用II型胶原（CII）免疫前鼻内给予热变性或胰蛋白酶消化的牛CII，可显著延迟CIA的发病，而给予天然CII则无此效果。给予变性或消化CII的小鼠抗CII IgG2a滴度远低于对照小鼠，而抗CII IgG1和IgG2b滴度未改变或略有降低。对CII和含有免疫显性T细胞决定簇的肽作出反应时，给予变性CII的小鼠的淋巴结细胞产生的干扰素-γ较少。这些结果表明，鼻内给予抗原优先下调Th1型反应，而未观察到Th2型反应增强。我们证明此处所示方法可能是类风湿关节炎的一种治疗方法。
