Kies M W
Adv Exp Med Biol. 1978;100:277-88. doi: 10.1007/978-1-4684-2514-7_20.
Experimental autoimmunity of the CNS has been well characterized--the antigen has been identified, effector cell specificity has been defined, and the relationship between cellular sensitization and antibody production has been partially clarified. In the guinea pig, experimental allergic encephalomyelitis (EAE) is induced by one injection of myelin basic protein in complete Freund's adjuvant (BP/CFA). If BP/CFA is preceded by repeated injections of basic protein in incomplete Freund's adjuvant (BP/IFA), EAE is not induced; the guinea pigs survive and ultimately produce antibody. Induction and prevention of EAE as well as antibody induction by this schedule are dependent on the presence of the intact encephalitogenic (T-cell) site in the polypeptide used for sensitization and preimmunization. In contrast, B cell sites (those peptide sequences which bind antibody) are independent of the T-cell site. At least 5 specific antigenic regions (B-cell sites) have been demonstrated in the BP molecule. High mycobacteria levels bypass the specificity requirement of helper T-cells but cannot bypass the specificity requirement of effector T-cells. In spite of the sophisticated immunologic techniques available, our knowledge of humoral and cellular sensitivity in multiple sclerosis (MS) patients is very limited. The experimental demonstration of an analogy between EAE and MS is weak: a) Demonstration of BP-sensitized cells or BP-specific antibodies in peripheral blood of MS patients has not been successful. b) Anti-myelin serum factors reported to be associated with both disease states (experimental autoimmunity and MS) are clearly not identical. Nevertheless, successful treatment of EAE in animals by BP/IFA injections has encouraged consideration of clinical trials to test the therapeutic value of BP injections in MS patients. If successful, the question will be answered: if unsuccessful, the dilemma still remains.
中枢神经系统的实验性自身免疫已得到充分表征——抗原已被鉴定，效应细胞特异性已被明确，细胞致敏与抗体产生之间的关系也已部分阐明。在豚鼠中，通过在完全弗氏佐剂（BP/CFA）中单次注射髓鞘碱性蛋白可诱发实验性变应性脑脊髓炎（EAE）。如果在BP/CFA之前先在不完全弗氏佐剂（BP/IFA）中反复注射碱性蛋白，则不会诱发EAE；豚鼠存活并最终产生抗体。EAE的诱导和预防以及按此方案诱导抗体均取决于用于致敏和预免疫的多肽中完整的致脑炎（T细胞）位点的存在。相比之下，B细胞位点（即与抗体结合的那些肽序列）与T细胞位点无关。在BP分子中已证实至少有5个特定的抗原区域（B细胞位点）。高浓度分枝杆菌绕过了辅助性T细胞的特异性要求，但不能绕过效应性T细胞的特异性要求。尽管有先进的免疫技术，但我们对多发性硬化症（MS）患者体液和细胞敏感性的了解非常有限。EAE与MS之间类比的实验证据不足：a）在MS患者外周血中未成功检测到BP致敏细胞或BP特异性抗体。b）据报道与两种疾病状态（实验性自身免疫和MS）相关的抗髓鞘血清因子显然并不相同。然而，通过BP/IFA注射成功治疗动物EAE鼓励了开展临床试验以测试BP注射对MS患者的治疗价值。如果成功，问题将得到解答；如果不成功，困境依然存在。
