Autoimmunity in multiple slcerosis: do we have an experimental model?
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.
D000276:Adjuvants, Immunologic; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control; D006168:Guinea Pigs; D006801:Humans; D007114:Immunization; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D004676:Myelin Basic Protein