Use of reinduced experimental autoimmune encephalomyelitis to evaluate the importance of epitope spread

Several investigators have reported experimental evidence of epitopespreading in experimental autoimmune encephalomyelitis (EAE). The role ofepitope spreading in the pathogenesis of relapsing or chronic autoimmunedisease is not established and the in vivo function of the T cells specificfor new epitopes which appear during an autoimmune response is unclear. Werecently demonstrated that mice which have recovered from an episode of EAEsuffer a relapse shortly after reinjection with the originalencephalitogen. The reinduced disease occurs in a reproducible fashion withan accelerated onset. This may be due to persistence of an expandedpopulation of previously activated encephalitogenic cells which are rapidlyreactivated when re-exposed to antigen. We reasoned that if epitope spreadproduces a significant number of encephalitogenic cells specific for a newepitope, then reinjection with that epitope should also cause the rapidonset of an episode of EAE. We tested this hypothesis using the knownencephalitogenic epitopes in SJL mice. After recovery from EAE induced withthe proteolipid protein peptide PLP139-151, five of 16 mice had anaccelerated relapse of EAE when reinjected with a second encephalitogenicpeptide, PLP178-191. All of the 10 mice reinjected with the originalPLP139-151 peptide relapsed. We conclude that epitope spread may produceencephalitogenic cells specific for new epitopes, but that the response tonew epitopes is minor compared to the response to the initial epitope.