Potent Mitogenic Activity of Staphylococcal Enterotoxin A Requires Induction of Interleukin 2

Abstract

Staphylococcal enterotoxin A (SEA), the most common cause of food poisoning, is capable of stimulating human T lymphocyte proliferation at concentrations as low as 10^––13 to 10^––16M. SEA also induces the lymphokines interleukin 2 (IL 2) and interferon gamma (IFNγ) at similarly low concentrations. HPL cultures were stimulated with SEA in the presence of antibodies to IL 2 to determine the possible role of this lymphokine in its potent mitogenic effects. Polyclonal and monoclonal antibodies to human IL 2 blocked SEA-induced mitogenesis. Treatment of cultures with higher concentrations of SEA overcame the anti-IL 2 blockage, corresponding to induction of higher concentrations of IL 2. Blockage of HPL mitogenesis by anti-IL 2 antibodies also resulted in inhibition of IFNγ production, which is dependent on IL 2. Neutralizing monoclonal antibody to IFNγ failed to block SEA-induced proliferation. The data indicate that the induction of IL 2, but not IFNγ, is a requirement for SEA induced lymphocyte proliferation. SEA food poisoning and IL 2 therapy for cancer result in similar toxic symptoms, characterized by malaise, fever, nausea or vomiting, and diarrhea. The similarity between SEA and IL 2 toxic effects, the fact that SEA is a potent inducer of lymphokines such as IL 2, and the fact that IL 2 induction is a prerequisite for the mitogenic effects of SEA raises the intriguing question of the role of lymphokines such as IL 2 in SEA-induced food poisoning.