Induction of experimental allergic encephalomyelitis in genetically resistant strains of mice

Abstract

Experimental allergic encephalomyelitis (EAE) is an acute autoimmune disease of the central nervous system. It is elicited in various laboratory animal species by a single injection of either whole central nervous system tissue homogenate, or the purified basic encephalitogenic protein isolated therefrom. Clinical manifestations of hind leg paralysis usually occur 11–21 days after challenge, preceded by histological lesions of perivascular infiltration in the brain1. EAE has been intensively investigated both as a model for human demyelinating diseases and as a prototypic organ-specific autoimmune disease1. EAE is under genetic control in guinea pigs, rats and mice, and strains that are genetically susceptible or resistant to EAE have been demonstrated2–4. We have previously5,6 investigated the genetic control of susceptibility to EAE in mice and demonstrated that the disease could be induced only in the SJL/J strain of mice, or in its crosses with various resistant strains. The resistance to EAE is not associated with genetic differences in the response of the various strains to pertussis vaccine, which is used as adjuvant in the induction of EAE in mice, as both the sensitive SJL/J strain and the resistant strains BALB/c, DBA/2 and C57BL/6J are responsive to pertussis7. A great difference was observed, however, in the sensitivity to EAE of the various F1 hybrids of SJL/J. Thus, crossing the sensitive SJL/J strain with part of the resistant strains, such as NZB, BALB/c or its congenic strains BALB . B10 and BALB. C3H, led to fully susceptible hybrids, with even higher incidence of EAE than that observed in the parental SJL/J strain. On the other hand, crossing SJL/J with other strains, such as C57BL/6J or DBA/2, led to hybrids with very low susceptibility to EAE. These results suggested that in the crosses with the various resistant BALB strains and NZB strain, there is probably complementation with another gene. It was therefore postulated that in these resistant strains, the influence of the gene determining susceptibility to EAE is masked by the presence of naturally occurring suppressor cells. We present here experimental evidence which corroborates this assumption.