A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

B A Jameson; J M McDonnell; J C Marini; R Korngold

doi:10.1038/368744a0

A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

B A Jameson, J M McDonnell, J C Marini, R Korngold

Thomas Jefferson University

Research output: Contribution to journal › Article › peer-review

147 Citations (Scopus)

Abstract

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). The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents, 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 antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.

Original language	English
Pages (from-to)	744-746
Number of pages	3
Journal	NATURE
Volume	368
Issue number	6473
DOIs	https://doi.org/10.1038/368744a0
Publication status	Published - 21 Apr 1994

Keywords

Amino Acid Sequence
Animals
Antigens, CD4
Drug Design
Encephalomyelitis, Autoimmune, Experimental
Humans
Magnetic Resonance Spectroscopy
Mice
Molecular Sequence Data
Peptides
T-Lymphocytes, Helper-Inducer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/368744a0

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title = "A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis",

abstract = "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). The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents, 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 antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.",

keywords = "Amino Acid Sequence, Animals, Antigens, CD4, Drug Design, Encephalomyelitis, Autoimmune, Experimental, Humans, Magnetic Resonance Spectroscopy, Mice, Molecular Sequence Data, Peptides, T-Lymphocytes, Helper-Inducer",

author = "Jameson, {B A} and McDonnell, {J M} and Marini, {J C} and R Korngold",

year = "1994",

month = apr,

day = "21",

doi = "10.1038/368744a0",

language = "English",

volume = "368",

pages = "744--746",

journal = "NATURE",

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TY - JOUR

T1 - A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

AU - Jameson, B A

AU - McDonnell, J M

AU - Marini, J C

AU - Korngold, R

PY - 1994/4/21

Y1 - 1994/4/21

N2 - 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). The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents, 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 antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.

AB - 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). The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents, 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 antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.

KW - Amino Acid Sequence

KW - Animals

KW - Antigens, CD4

KW - Drug Design

KW - Encephalomyelitis, Autoimmune, Experimental

KW - Humans

KW - Magnetic Resonance Spectroscopy

KW - Mice

KW - Molecular Sequence Data

KW - Peptides

KW - T-Lymphocytes, Helper-Inducer

U2 - 10.1038/368744a0

DO - 10.1038/368744a0

M3 - Article

C2 - 8152486

SN - 0028-0836

VL - 368

SP - 744

EP - 746

JO - NATURE

JF - NATURE

IS - 6473

ER -

A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

Abstract

Keywords

UN SDGs

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