ACTIVATION AND CLONAL EXPANSION OF HUMAN MYELIN BASIC PROTEIN-REACTIVE T-CELLS BY BACTERIAL SUPERANTIGENS

Autoreactive T cells specific for myelin basic protein (MBP) are part of the normal T cell repertoire and are present both in patients with multiple sclerosis (MS) and healthy individuals. There is evidence sug gesting in vivo activation and persistent clonal expansion of MBP-reac tive T cells in MS. This study was undertaken to investigate the poten tial role of bacterial superantigens (SA) in the activation of MBP-rea ctive T cells. Twenty-seven MBP-reactive T cell clones generated from 10 MS patients and one normal individual were examined for reactivity to SA, in association with their T cell receptor V beta gene usage. Th e majority of the clones responded to at least one of the SA tested, s taphylococcal enterotoxins (SEA and SEB) and toxic shock syndrome toxi n-1 (TSST-1). The clones reactive to SEA and SEB expressed various V b eta genes while T cell reactivity to TSST-1 correlated with the V beta 2 expression. Furthermore, circulating MBP-reactive T cells could be expanded from lymphocyte cultures primarily exposed to respective SA i n more than 50% of MS patients and normal individuals tested. However, activation and expansion of circulating MBP-reactive T cells by SA wa s not directly associated with the disease. This study lends support t o the potential role of SA in the activation of MBP-reactive T cells a nd suggests that an altered regulatory mechanism may account for furth er expansion and persistence of MBP-reactive T cells in MS. (C) 1995 A cademic Press Limited