Follicular helper T cells mediate IgE antibody response to airborne allergens

Background T_H2 cells have long been believed to play a pivotal role in allergic immune responses, including IgE antibody production and type 2 cytokine–mediated inflammation and pathology. A new T-cell subset, follicular helper T (T_FH) cells, is specialized in supporting B-cell maturation and antibody production. Objective We sought to investigate the roles of T_FH cells in allergic immune responses. Methods Naive mice were exposed to cytokines or natural allergens through the airways. Development of allergic immune responses was analyzed by collecting draining lymph nodes and sera and by challenging the animals. Cytokine reporter mice and gene-deficient mice were used to dissect the immunologic mechanisms. Results We observed the development of IL-4–producing T_FH cells and T_H2 cells in draining lymph nodes after airway exposure to IL-1 family cytokines or natural allergens. T_FH and T_H2 cells demonstrated unique phenotypes, tissue localization, and cytokine responses. T_FH cells supported the sustained production of IgE antibody in vivo in the absence of other T-cell subsets or even when T_H2 cell functions were severely compromised. Conversely, conditional deficiency of the master regulator Bcl6 in CD4⁺ T cells resulted in a marked reduction in T_FH cell numbers and IgE antibody levels, but type 2 cytokine responses and eosinophilic inflammation in the airways remained unaffected. Conclusion T_FH cells play critical roles in the regulation of IgE antibody production. Allergic immune responses to airborne allergens likely involve 2 distinct subsets of IL-4–producing CD4⁺ T cells, namely T_FH and Th2 cells.