Identification of a T follicular helper cell subset that drives anaphylactic IgE.

Cross-linking of high-affinity immunoglobulin E (IgE) results in the life-threatening allergic reaction anaphylaxis. Yet the cellular mechanisms that induce B cells to produce IgE in response to allergens remain poorly understood. T follicular helper (T) cells direct the affinity and isotype of antibodies produced by B cells. Although T cell-derived interleukin-4 (IL-4) is necessary for IgE production, it is not sufficient. We report a rare population of IL-13-producing T cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity. These "T13" cells have an unusual cytokine profile (IL-13IL-4IL-5IL-21) and coexpress the transcription factors BCL6 and GATA3. T13 cells are required for production of high- but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking T13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.