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 suggesting in vivo activation and persistent clonal expansion of MBP-reactive T cells in MS. This study was undertaken to investigate the potential role of bacterial superantigens (SA) in the activation of MBP-reactive 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. The majority of the clones responded to at least one of the SA tested, staphylococcal enterotoxins (SEA and SEB) and toxic shock syndrome toxin-1 (TSST-1). The clones reactive to SEA and SEB expressed various V beta 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 in more than 50% of MS patients and normal individuals tested. However, activation and expansion of circulating MBP-reactive T cells by SA was not directly associated with the disease. This study lends support to the potential role of SA in the activation of MBP-reactive T cells and suggests that an altered regulatory mechanism may account for further expansion and persistence of MBP-reactive T cells in MS.
D000328:Adult; D001427:Bacterial Toxins; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004768:Enterotoxins / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D000939:Epitopes; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal