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

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 (TEM) 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 TH17/TC17 and TH1 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.

► We studied secretion of IL-17A by CD4 + and CD8 + T cells to direct TCR stimulation. ► IL-17A-secreting T cells are multifunctional, co-expressing IFN-γ, TNF-α and IL-2. ► Multifunctional IL-17A + cells express markers of TH17/TC17 and TH1 subsets. ► Unsupervised FLOCK analysis uncovered additional distinct IL-17A + populations. ► IL-17A multifunctional T cells are likely to play a role in the pathogenesis of TSS.