THE CASE AGAINST EPITOPE SPREAD IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

Citation
K. Takacs et Dm. Altmann, THE CASE AGAINST EPITOPE SPREAD IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS, Immunological reviews, 164, 1998, pp. 101-110
Citations number
40
Categorie Soggetti
Immunology
Journal title
ISSN journal
01052896
Volume
164
Year of publication
1998
Pages
101 - 110
Database
ISI
SICI code
0105-2896(1998)164:<101:TCAESI>2.0.ZU;2-B
Abstract
Epitope spread has been proposed as a possible mechanism for diversifi cation of the autoimmune T-cell response during disease. Specifically, it offers a plausible mechanism for the previously obscure cyclical n ature of autoimmune demyelination whereby the sequence of attack, quie scence and reactivation may recur over a long period of time. However, we were concerned that previous studies of epitope spread have not ne cessarily shown it to be well correlated with disease severity or rela pse. Furthermore, we had studied two transgenic models of exacerbated experimental allergic encephalomyelitis (EAE) in which no indication o f spread away from the initial disease-inducing peptide could be obser ved. We conducted a systematic, longitudinal study in SJL mice to look for determinant spread during relapsing and remitting EAE, correlatin g epitope recognition and cytokine production with disease severity. W hen T cells from spleen, lymph node and central nervous system (CNS) w ere analysed, little or no determinant spread was found. The best immu nological correlate of relapse was the reappearance after remission of CNS-infiltrating T cells mounting a strong proliferative and interfer on (IFN)-gamma response to the original disease-inducing epitope. Our data do not support a general role for determinant spread in EAE relap se. Rather, they indicate the importance of a focused proliferative an d IFN-gamma response to the disease-inducing peptide.