Successful prevention and treatment of autoimmune encephalomyelitis by short-term administration of anti-T-cell receptor alpha beta antibody.
To identify an effective immunotherapy for T-cell-mediated autoimmune diseases, prevention and treatment of experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats was attempted by administering a monoclonal antibody (mAb), R73, which is specific for rat T-cell receptor (TcR) alpha beta. Short-term administration of R73 at relatively low doses before immunization with encephalitogenic antigen, myelin basic protein (MBP), prevented the development of EAE. However, treatment with anti-CD4 and anti-Ia mAb in the same protocol was ineffective. Flow cytometric analysis demonstrated that short-term administration of R73 resulted in transient down-regulation of the TcR molecules, whereas the number of CD2-expressing T cells was well preserved. Furthermore, the response to MBP of T cells isolated from rats that were pretreated with R73 and then immunized with MBP was strongly suppressed. On the other hand, the T-cell response of R73-pretreated rats to a third-party antigen which was immunized at a later period was not inhibited. These findings suggest that in vivo administration of a low dose of R73 protects rats from EAE by inducing anergy of MBP-reactive encephalitogenic T cells. Furthermore, R73 treatment which started on day 10 of the immunization (shortly before the day of onset of clinical signs) completely suppressed the induction of EAE and that which started on day 11 (the day of onset) hastened recovery. Since the phenotypes of the TcR V beta chain of encephalitogenic T cells are not so limited as previously believed, immunotherapy with mAb against the TcR alpha beta framework may be one of the best methods for treatment of T-cell-mediated autoimmune diseases.
Matsumoto
Y
Y
Department of Immunology, Niigata University School of Medicine, Japan.
Tsuchida
M
M
Hanawa
H
H
Abo
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000517:prevention & control / Q000628:therapy*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control / Q000628:therapy*; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta