Unexpected heterogeneity of multifunctional T cells in response to superantigen stimulation in humans

Abstract

Toxic shock syndrome (TSS) is a potentially life threatening condition characterized by fever, rash, shock, and multi-organ failure. Staphylococcal enterotoxin B (SEB) is a well characterized superantigen that has been shown to play an important role in TSS. Although the precise mechanisms by which SEB and other superantigens cause TSS are unknown, induction of a pro-inflammatory cytokine cascade appears central to this phenomenon. We show that CD4+ and CD8+ Teffector/memory (T(EM)) and other subsets produce IL-17A following SEB stimulation. We also show that IL-17A is co-produced with other pro-inflammatory cytokines (i.e., IL-2, IFN-γ and TNF-α). These responses are significantly different than those elicited by mitogenic stimulation. Multifunctional IL-17A producing cells possess markers typical of the T(H)17/T(C)17 and T(H)1 subsets, including CCR6, IL-22, and transcription factors retinoic acid receptor-related orphan nuclear receptor (ROR)-γt and T-bet. These results suggest a possible role for IL-17A-producing multifunctional T cells in the pathogenesis of TSS.