| Abstract: | Monoclonal antibodies (mAbs) directed against the Vβ 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-Vβ 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 Vβ2 and Vβ17 during acute and relapsing disease. T cell lines specific for PLP 139–151 were magnetically sorted to express 80–90% Vβ2. These Vβ2-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% Vβ2 were treated with anti-Vβ2 mAb. Anti-Vβ2 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-Vβ mAbs showed only a mild clinical effect on R-EAE induced by immunization with PLP 139–151 or R-EAE induced by immunization with PLP 139–151 or R-EAE transferred by a PLP 139–151-specific T cell line expressing multiple Vβs. A cocktail of mAbs directed against Vβ2, Vβ4, and Vβ17 significantly reduced the numbers of spinal cord T cells expressing these Vβs during acute EAE but had little effect on disease course, suggesting that pathogenic T cells expressing other Vβs were producing disease. These findings may have implications for the treatment of multiple sclerosis with Vβ-selective therapy. © 1996 Wiley-Liss, Inc. |
