STAPHYLOCOCCAL-ENTEROTOXIN B-INDUCED T-CELL ANERGY IS MEDIATED BY REGULATORY T-CELLS

Naive T cells mount a vigorous proliferative response to superantigen (SAg) stimulation in vivo. The proliferative response is followed by a partial deletion of responder T cells. Part of the deletion process h as recently been attributed to the action of regulatory cytotoxic T ce lls that recognize major histocompatibility complex (MHC) class I-asso ciated antigen receptor determinants on the target cell surface. Respo nder T cells that survived the SAg response were found to be incapable of generating a secondary proliferative response to a SAg challenge. We show here that this 'anergy' is enforced by CD8-positive regulatory suppressive T cells. These regulatory cells inhibit cell division of preactivated T cells but not the SAg response of naive T cells. Regula tory T cells are not generated in the presence of cyclosporin A and, o nce activated, become inactivated or deleted when restimulated in the presence of this immunosuppressive drug.