Prevention and Treatment of Murine Experimental Allergic Encephalomyelitis

Experimental allergic encephalomyelitis (EAE)' is an autoimmune disease of the central nervous system (CNS) that is induced by immunization of susceptible animal strains with myelin basic protein (MBP). The disease is characterized by lymphocyte infiltration leading to CNS lesions, demyelination, and chronic relapsing paralysis, which are symptoms similar to those seen for multiple sclerosis (MS) in humans (1-6). Prevention of EAE by treatment with CD4-specific antibodies (7, 8) and adoptive transfer of disease symptoms with MBP-specific T helper (Th) cells (9-16) have implicated CD4+ Th cells as the primary disease-inducing component of EAE. The dominant T cell response to MPB in mice of particular MHC haplotypes is directed towards distinct MBP determinants (16-20). For example, B10.PL and PL/J mice (H-2°) respond primarily to an acetylated NH2-terminal epitope, while SJL/J mice (H-2g) respond primarily to a more COOH-terminal epitope. Recent studies have indicated that in H-2u mice the T cell response to the dominant NH2terminal epitope of MBP is of limited heterogeneity (21-23). Molecular characterization of the TCRs used by B10.PL-derived Th cells revealed the use of only two distinct V/3 gene segments, V/38.2 and VS13, and two distinct Va gene segments, Va2.3 and Va4.3 (21) . The gene products of either V/3 segment can pair with the gene products ofeither Va segment to yield a total of four discrete types ofTh cells . The majority of Th cells examined expressed the V08.2 gene segment (84%) while the remainder expressed the V013 gene segment (16%). The distribution ofVa gene segments was less skewed among these MBP-specific Th cells with 60% expressing Va2 .3 and 40% expressing Va4.3 . Thelimited use of TCRV region genes in the response to MBP allows the application of unique strategies of specific immune intervention . Since the majority of MBP NH2-terminal reactive Th cells in H-2u mice use V08.2, mAbs to V08 (F23 .1,