Differential susceptibility to experimental allergic encephalomyelitis (EAE) in genetically defined A+ and A- rabbits

Only one out of 57 A-/A- rabbits immunized with rat or guinea-pig myelin developed clinical signs suggestive of EAE. On the contrary, clinical signs of acute or chronic EAE were found in two thirds of the 102 A+/A+ and A+/A- rabbits immunized in the same way. About one third of the diseased animals had reversible acute EAE, another third died paralysed and the last third developed chronic progressive or relapsing EAE. Incidence and severity of EAE symptoms were positively correlated with age and no significant difference was observed between males and females. Cellular and humoral anti-myelin responses were stronger in A+ than in A- rabbits. Anti-A antibodies, on the contrary, were only detected in A- rabbits. The A+ rabbits did not make Anti-A at any time. Anti-A antibodies increased early, in A- rabbits, after immunization with myelin (11-30 days) and were later replaced by a low, but specific, anti-myelin response (60-90 days). The gene responsible for the susceptibility to EAE is autosomal and dominant over resistance. This gene must be closely linked to the A locus or might be the A gene itself. The low susceptibility of A- rabbits to the disease could be, in this last case, a consequence of the competition between the early anti-A and the normal anti-myelin immune responses, both induced by the injection of myelin.