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

抄録

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 (T_FH) cell subset, designated T_FH2 cells, which is tightly associated with the production of high-affinity IgE antibodies. T_FH2 cells had a transcriptionally hybrid phenotype between T_H2 and T_FH 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 (T_H2) cells were capable of differentiating into T_FH2 cells upon secondary antigen stimulation. The type 2 T_FH (T_FH2) conversion process was entirely attenuated in T cell-specific deficient mice of Bcl6 (Bcl6^f/f cd4-cre; Bcl6^ΔT). Moreover, the transfer of IL-13 defective T_H2 cells partially inhibited IgE responses and significantly decreased the high-affinity IgE, even though T_FH development was intact. Therefore, IL-13 from T_FH2 cells controlled the selective enrichment of IgE⁺ B-cells with a high affinity for allergens. A previously undefined unique T_FH subset, T_FH2, likely contributes to IgE responses. This suggests that the accumulation of antigen-specific T_H2 cells in human patients with allergies is a high-risk factor for IgE-dependent allergic diseases.