title: The case against epitope spread in experimental allergic encephalomyelitis.
abstract: Epitope spread has been proposed as a possible mechanism for diversification of the autoimmune T-cell response during disease. Specifically, it offers a plausible mechanism for the previously obscure cyclical nature of autoimmune demyelination whereby the sequence of attack, quiescence and reactivation may recur over a long period of time. However, we were concerned that previous studies of epitope spread have not necessarily shown it to be well correlated with disease severity or relapse. Furthermore, we had studied two transgenic models of exacerbated experimental allergic encephalomyelitis (EAE) in which no indication of spread away from the initial disease-inducing peptide could be observed. We conducted a systematic, longitudinal study in SJL mice to look for determinant spread during relapsing and remitting EAE, correlating epitope recognition and cytokine production with disease severity. When T cells from spleen, lymph node and central nervous system (CNS) were analysed, little or no determinant spread was found. The best immunological correlate of relapse was the reappearance after remission of CNS-infiltrating T cells mounting a strong proliferative and interferon (IFN)-gamma response to the original disease-inducing epitope. Our data do not support a general role for determinant spread in EAE relapse. Rather, they indicate the importance of a focused proliferative and IFN-gamma response to the disease-inducing peptide.
authors.affiliation: MRC Clinical Sciences Centre, ICSM, Hammersmith Hospital, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Takács
authors.forename: D M
authors.initials: DM
authors.lastname: Altmann
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology*; D000939:Epitopes; D051379:Mice; D010507:Periodicity; D012008:Recurrence; D013154:Spleen / Q000276:immunology
chemical_list: D016207:Cytokines; D000939:Epitopes