Immunization method influences EAE relapse rate in SJL mice (171.6)

Abstract

Abstract We have discovered that administration of pertussis toxin as an adjuvant during induction of experimental autoimmune encephalomyelitis (EAE) in SJL mice results in a more severe first EAE wave, but fewer, milder and later relapses than if pertussis toxin is not used. This finding is inconsistent with the widely-accepted epitope spreading hypothesis, which predicts more severe relapses resulting from more severe tissue damage in the first wave. EAE in SJL mice immunized with PLP139-151/CFA is the mouse model which most closely resembles human remitting/relapsing multiple sclerosis. EAE develops in 90-100% of immunized mice 10-15 days after immunization. The first wave of EAE lasts several days and most mice recover from it. After a disease-free period from one day to several months, most mice relapse. 50-75% of mice develop a relapse during the first 6 weeks after immunization. It is not clear why relapses develop. It is widely accepted that relapses result from epitope spreading - new immune responses to epitopes of self antigens other than the PLP139-151. It is believed that tissue damage from the initial immune response allows “presentation” of new epitopes to auto-reactive T cells. Our findings appear to conflict with this hypothesis. Potential mechanisms of relapse suppression by pertussis toxin will be discussed.