Treatment of relapsing autoimmune encephalomyelitis with T cell receptor V beta-specific antibodies when proteolipid protein is the autoantigen.
Monoclonal antibodies (mAbs) directed against the V beta chain of the T cell receptor (TCR) of pathogenic T cells have been used to treat acute murine experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (BP). We evaluated anti-V beta mAb for the treatment of relapsing EAE (R-EAE) induced in SJL/J mice by the myelin proteolipid protein (PLP) peptide 139-151. Spinal cord mononuclear cells isolated from mice immunized for R-EAE with PLP 139-151 were shown to express a predominance of V beta 2 and V beta 17 during acute and relapsing disease. T cell lines specific for PLP 139-151 were magnetically sorted to express 80-90% V beta 2. These V beta 2-enriched lines induced typical relapsing demyelinating EAE in naive recipient mice. SJL/J mice with R-EAE induced by a PLP 139-151-specific T cell line expressing 88% V beta 2 were treated with anti-V beta 2 mAb. Anti-V beta 2 mAb markedly reduced clinical and histological disease severity when given at the time of cell transfer or when given at clinical disease onset. In contrast, anti-V beta mAbs showed only a mild clinical effect on R-EAE induced by immunization with PLP 139-151 or R-EAE transferred by a PLP 139-151-specific T cell line expressing multiple V beta s. A cocktail of mAbs directed against V beta 2, V beta 4, and V beta 17 significantly reduced the numbers of spinal cord T cells expressing these V beta s during acute EAE but had little effect on disease course, suggesting that pathogenic T cells expressing other V beta s were producing disease. These findings may have implications for the treatment of multiple sclerosis with V beta-selective therapy.
Whitham
R H
RH
Veterans Administration Medical Center, Portland, Oregon 97207, USA.
Wingett
D
D
Wineman
J
J
Mass
M
M
Wegmann
K
K
Vandenbark
A
A
Offner
H
H
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001324:Autoantigens / Q000276:immunology*; D002460:Cell Line; D017931:DNA Primers; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D005260:Female; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D017931:DNA Primers; D018991:Myelin Proteolipid Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta