Type 2 helper T cells convert into Interleukin-13-expressing follicular helper T cells after antigen repriming

Anaphylaxis caused by allergen sensitization and vaccination is a serious health concern. The severity of anaphylaxis is associated with the presence of immunoglobulin E (IgE) antibodies that bind to allergens with a high affinity. Here, we report the development of a unique Interleukin-13 (IL-13)-producing follicular helper T (TFH) cell subset, designated TFH2 cells, which is tightly associated with the production of high-affinity IgE antibodies. TFH2 cells had a transcriptionally hybrid phenotype between TH2 and TFH cells, which express GATA-binding protein 3 (Gata3) and B-cell/CLL lymphoma 6 (BCL-6), respectively. Adaptive transfer experiments demonstrated that type 2 helper T (TH2) cells were capable of differentiating into TFH2 cells upon secondary antigen stimulation. The type 2 TFH (TFH2) conversion process was entirely attenuated in T cell-specific deficient mice of Bcl6 (Bcl6f/f cd4-cre; Bcl6ΔT). Moreover, the transfer of IL-13 defective TH2 cells partially inhibited IgE responses and significantly decreased the high-affinity IgE, even though TFH development was intact. Therefore, IL-13 from TFH2 cells controlled the selective enrichment of IgE+ B-cells with a high affinity for allergens. A previously undefined unique TFH subset, TFH2, likely contributes to IgE responses. This suggests that the accumulation of antigen-specific TH2 cells in human patients with allergies is a high-risk factor for IgE-dependent allergic diseases.