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| A predictable sequential determinant spreading cascade invariably accompanies progression of experimental autoimmune encephalomyelitis: A basis for peptide-specific therapy after onset of clinical disease |
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| Author(s): Yu M, Johnson JM, Tuohy VK |
| Source: JOURNAL OF EXPERIMENTAL MEDICINE Volume: 183 Issue: 4 Pages: 1777-1788 Published: APR 1 1996 |
| Times Cited: 191 References: 54 |
| Abstract: The development of autoimmune disease is accompanied by tile acquired recognition of new self-determinants, a process commonly referred to as determinant spreading. In this study, we addressed the question of whether determinant spreading is pathogenic for progression of chronic-relapsing experimental autoimmune encephalomyelitis (EAE), a disease with many similarities to multiple sclerosis (MS). Our approach involved a systematic epitope mapping of responses to myelin proteolipid protein (PLP) as well as assaying responses to known encephalitogenic determinants of myelin basic protein (MBP 87-99) and myelin oligodendrocyte glycoprotein (MOG 92-106) at various times after induction of EAE in (SWR X SJL)F-1 mice immunized with PLP 139-151. We found that the order in which new determinants are recognized during the course of disease follows a predictable sequential pattern. At monthly intervals after immunization with p139-151, responses to PLP 219-273, MBP 87-99, and PLP 173-198 were sequentially accumulated in all mice examined. Three lines of evidence showed that determinant spreading is pathogenic for disease progression: (a) spreading determinants mediate passive transfer of acute EAE, in naive (SWR X SJL)F-1 recipients; (b) an invariant relationship exists between the development of relapse/progression and tile spreading of recognition to new immunodominant encephalitogenic determinants; and (c) after EAE onset, the induction of peptide-specific tolerance to spreading but not to nonspreading encephalitogenic determinants prevents subsequent progression of EAE. Thus, tile predictability of acquired self-determinants recognition provides a basis for sequential determinant-specific therapeutic intervention after onset of the autoimmune disease process. |
| Document Type: Article |
| Language: English |
Addresses:
1. CLEVELAND CLIN FDN, DEPT IMMUNOL, RES INST, CLEVELAND, OH 44195 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021 |
| Subject Category: Immunology; Medicine, Research & Experimental |
| IDS Number: UH144 |
| ISSN: 0022-1007 |
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