Induction of interleukin-1 in human monocytes by the superantigen Staphylococcal Enterotoxin A requires the participation of T cells

Abstract

Nanogram quantities of the bacterial superantigen Staphylococcal Enterotoxin A (SEA) induced significant amounts of extracellular IL-1α and IL-1β in human peripheral blood mononuclear cells. Induction of maximal IL-1α and IL-1β levels by lipopolysaccharide (LPS) required microgram quantities. LPS induced detectable extracellular IL-1 content within 3–6 hr and maximal levels were detected already after 12 hr. Induction of IL-1 production by SEA showed a delayed release with peak values after 24–48 hr. IL-1β was the major species of IL-1 seen in both SEA- and LPS-stimulated culture supernatants. SEA was in general a relatively stronger inducer of extracellular IL-1α than LPS. SEA-induced extracellular IL-1 production in human monocytes was entirely dependent on the presence of T cells, whereas addition of T cells to LPS-stimulated purified human monocytes only marginally enhanced the extracellular IL-1 production. The capacity to induce extracellular IL-1 production in monocytes in response to SEA was high in the CD4 + 45RO + memory T cell subset, whereas CD4 + 45RA + naive T cells and CD8 + T cells had lower IL-1-inducing capacity. The T cell help for IL-1 production could not be replaced by a panel of T cell-derived recombinant lymphokines added to SEA-stimulated monocytes, including IFN-γ and TNF, indicating the participation of cell membrane-bound ligands or hitherto unidentified Soluble mediators.