A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

EXPERIMENTAL allergic encephalomyelitis (EAE) is an acute inflammatory autoimmune disease of the central nervous system that can be elicited in rodents and is the major animal model for the study of multiple sclerosis (MS) 1,2 . The pathogenesis of both EAE and MS directly involves the CD4 + helper...

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Bibliographic Details
Published in:Nature (London) 1994-04, Vol.368 (6473), p.744-746
Main Authors: Jameson, Bradford A, McDonnell, James M, Marini, Joseph C, Korngold, Robert
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animal models
Animals
Biological and medical sciences
Cancer
CD4 Antigens - chemistry
CD4 Antigens - therapeutic use
Central nervous system
Drug Design
Encephalomyelitis, Autoimmune, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - prevention & control
Humanities and Social Sciences
Humans
Immunogenicity
Immunomodulators
Injection
letter
Magnetic Resonance Spectroscopy
Medical research
Medical sciences
Mice
Molecular Sequence Data
multidisciplinary
Peptides - chemical synthesis
Peptides - therapeutic use
Pharmacology. Drug treatments
Rodents
Science
Science (multidisciplinary)
T-Lymphocytes, Helper-Inducer - immunology
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Summary:EXPERIMENTAL allergic encephalomyelitis (EAE) is an acute inflammatory autoimmune disease of the central nervous system that can be elicited in rodents and is the major animal model for the study of multiple sclerosis (MS) 1,2 . The pathogenesis of both EAE and MS directly involves the CD4 + helper T-cell subset 3–5 . Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents 6–9 , and are currently being used in human clinical trials for MS. We report here that similar therapeutic effects can be achieved in mice using a small (rationally designed) synthetic analogue of the CD4 protein surface. It greatly inhibits both clinical incidence and severity of EAE with a single injection, but does so without depletion of the CD4 + subset and without the inherent immunogenicity of an antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.
ISSN:0028-0836
1476-4687
DOI:10.1038/368744a0