Bacterial toxin superantigens activate human T lymphocytes reactive with myelin autoantigens

Some bacteria that are common human pathogens produce protein toxins that are potent activators of human T lymphocytes expressing certain types of T-cell receptors. In this study we examined the ability of staphylococcal toxins to stimulate human T lymphocytes that also recognized the myelin autoantigens myelin basic protein and proteolipid protein. T-cell populations responding to myelin basic protein or proteolipid protein were isolated from 4 subjects including 1 individual with multiple sclerosis. All myelin antigen-specific T cells responded in proliferation studies to at least one of the nine superantigenic toxins used in this study. The superantigenic toxins were up to 7 x 10(5)-fold more potent in proliferation assays than the myelin antigens to which the T cells were initially sensitized. In addition, cytotoxic, myelin basic protein-reactive T lymphocytes lysed antigen-presenting cells incubated with superantigenic toxins. These findings demonstrate a mechanism by which some bacterial infections might produce activation of myelin basic protein- and proteolipid protein-reactive T lymphocytes and perhaps contribute to demyelinating disease in humans.