Jonker M, van Lambalgen R, Mitchell D J, Durham S K, Steinman L
TNO Primate Center, Rijswijk, The Netherlands.
J Autoimmun. 1988 Oct;1(5):399-414. doi: 10.1016/0896-8411(88)90064-9.
Experimental Allergic Encephalomyelitis (EAE) was induced in rhesus monkeys by subcutaneous immunization with calfbrain homogenate in complete Freunds adjuvant. Monkeys were treated with major histocompatibility complex (MHC) Class II specific monoclonal antibodies (MoAb) as soon as the first clinical EAE signs became apparent. Two different treatments were tested. One consisted of 10 daily injections of a mixture of two MHC Class II specific MoAb, reactive with a monomorphic structure of rhesus monkey Class II molecules. The other consisted of 10 daily injections of Genox3.53, specific for HLA-DQW1. This MoAb crossreacts well with monkeys and also detects a polymorphism in this species and is presumably reactive with the RhLA-DQW1 antigen. Both MoAb treatments could modify the clinical course of EAE favourably. Untreated animals invariably died within 3 d of the onset of clinical EAE signs. Only one of the three monkeys treated with the monomorphic MHC Class II MoAb preparation died within 3 d, and the other two survived significantly longer than untreated animals. Both animals treated with Genox3.53 survived significantly longer than untreated control animals. Although only a few animals were tested, these results clearly show the possible beneficial influence of MHC Class II specific MoAb on a T-cell mediated autoimmune disease.
通过在完全弗氏佐剂中皮下注射小牛脑匀浆,在恒河猴中诱导实验性变应性脑脊髓炎(EAE)。一旦出现首个临床EAE体征,就用主要组织相容性复合体(MHC)II类特异性单克隆抗体(MoAb)对猴子进行治疗。测试了两种不同的治疗方法。一种是连续10天每天注射两种MHC II类特异性MoAb的混合物,这两种MoAb与恒河猴II类分子的单态结构发生反应。另一种是连续10天每天注射针对HLA - DQW1的Genox3.53。这种MoAb与猴子有良好的交叉反应,还能检测该物种中的一种多态性,推测它与RhLA - DQW1抗原发生反应。两种MoAb治疗均能有利地改变EAE的临床病程。未经治疗的动物在临床EAE体征出现后3天内 invariably 死亡。用单态MHC II类MoAb制剂治疗的三只猴子中只有一只在3天内死亡,另外两只存活时间明显长于未经治疗的动物。用Genox3.53治疗的两只动物存活时间均明显长于未经治疗的对照动物。尽管只测试了少数动物,但这些结果清楚地表明MHC II类特异性MoAb对T细胞介导的自身免疫性疾病可能具有有益影响。