Use of reinduced experimental autoimmune encephalomyelitis to evaluate the importance of epitope spread.
Several investigators have reported experimental evidence of epitope spreading in experimental autoimmune encephalomyelitis (EAE). The role of epitope spreading in the pathogenesis of relapsing or chronic autoimmune disease is not established and the in vivo function of the T cells specific for new epitopes which appear during an autoimmune response is unclear. We recently demonstrated that mice which have recovered from an episode of EAE suffer a relapse shortly after reinjection with the original encephalitogen. The reinduced disease occurs in a reproducible fashion with an accelerated onset. This may be due to persistence of an expanded population of previously activated encephalitogenic cells which are rapidly reactivated when re-exposed to antigen. We reasoned that if epitope spread produces a significant number of encephalitogenic cells specific for a new epitope, then reinjection with that epitope should also cause the rapid onset of an episode of EAE. We tested this hypothesis using the known encephalitogenic epitopes in SJL mice. After recovery from EAE induced with the proteolipid protein peptide PLP139-151, five of 16 mice had an accelerated relapse of EAE when reinjected with a second encephalitogenic peptide, PLP178-191. All of the 10 mice reinjected with the original PLP139-151 peptide relapsed. We conclude that epitope spread may produce encephalitogenic cells specific for new epitopes, but that the response to new epitopes is minor compared to the response to the initial epitope.
Department of Neurology, University of Texas--Houston Health Science Center, 77030, USA.
J W
JW
Lindsey
D000367:Age Factors; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology; D018929:Cell Culture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D004676:Myelin Basic Protein; D011510:Proteolipids / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000939:Epitopes; D004676:Myelin Basic Protein; D011510:Proteolipids