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). 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.
Jameson
B A
BA
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia 19107.
McDonnell
J M
JM
Marini
J C
JC
Korngold
R
R
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000627:therapeutic use; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D015704:CD4 Antigens; D010455:Peptides