The Staphylococcal Toxic Shock Syndrome

Toxic shock syndrome toxin 1 (TSST1)t is a 22-kD exotoxin produced by most strains ofStaphylococcus aureus isolated from patients with toxic shock syndrome (TSS) (1) . TSST1 is a potent activator of monocytes and T cells . It acts on monocytes to induce the synthesis of IL-1 and TNF (2-4) . TSSTl also triggers T cell activation and proliferation (5), as well as the production of large amounts of various lymphokines such as IL-2 (6) and IFN-y (7) . The massive induction of monokine and lymphokine production by TSST1 is thought to play an important role in the pathogenesis of TSS. A significant insight into the mechanism ofaction ofTSST1, as well as other related staphylococcal exotoxins, came with the observation that these toxins bind directly to MHC class II molecules (8-11). Among the MHC class II molecules, TSST1 binds equally well with high affinity and saturation kinetics to HLA-DR and -DQ antigens (8) . TSST1 also binds to HLA-DP alleles, albeit with a much lower affinity than is observed for HLA-DR and -DQalleles (Scholl, P, unpublished data) . The MHC class II-bound toxin behaves as a superantigen that interacts with T cells via the TCR )3 chain (12, 13) to induce MHC-unrestricted T cell activation and proliferation . The ability ofMHC class II-bound TSST1 to engage T cells raises the possibility that TSST1 may mimic nominal antigen in initiating cognate interaction between T and B cells resulting in B cell proliferation and Ig production . We demonstrate here that TSST1 induces both the proliferation of resting human B cells and their differentiation into Ig-secreting lymphocytes . Triggering of B cell proliferation and differentiation by TSST1 is dependent on the presence of T cells, and proceeds via