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 ac ute murine experimental autoimmune encephalamyelitis (EAE) induced by myelin basic protein (BP). The evaluated anti-V beta mAb, for the trea tment of relapsing EAE (R-EAE) induced in SJL/J mice by the myelina pr oteolipid 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 rel apsing disease. T cell lines specific for PLP 139-151 were magneticall y sorted to express 80-90% V beta 2. These V beta 2-enriched lines ind uced typical relapsing demyelinating EAE in naive recipient mice. SJL/ J mice with R-EAE induced by a PLP 139-151-specific T cell line expres sing 88% V beta 2 were treated with anti-V beta 2 mAb. Anti-V beta 2 m Ab markedly reduced clinical and histological disease severity when gi ven at the time of cell transfer or when given at clinical disease ons et. In contrast, anti-V beta mAbs showed only a mild clinical effect. an 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 s ignificantly reduced the numbers of spinal cord T cells expressing the se V beta s during acute EAE hut had little effect on disease course, suggesting that pathogenic T cells expressing other V beta s were prod ucing disease. These findings may have implications for the treatment of multiple sclerosis with V beta-selective therapy. (C) 1996 Wiley-Li ss, Inc.