Regulatory T Cells Induced by Mucosal B Cells Alleviate Allergic Airway Hypersensitivity

Asthma is one of the most common chronic airway inflammatory diseases. The induction of immunologic tolerance via mucosa has been used for treating allergic diseases. B cells, which comprise the major cell population in Peyer's patches, were shown to induce the development of regulatory T (Treg) cells. This study investigated the role of B cells in Peyer's patches regarding the induction of tolerance and Treg cell functions. An in vitro suppressive assay and ELISA were used to evaluate the function of T cells stimulated by Peyer-patch B cells (Treg-of-B cells). The therapeutic potential of Treg-of-B cells was then evaluated by an animal model of airway inflammation. Treg-of-B cells were found to exert a suppressive function on T-cell proliferation. Antigen-loaded B cells isolated from Peyer's patches were more tolerogenic, and had the potential to generate more suppressive Treg-of-B cells via the production of IL-10 and cell-cell contacts. Treg-of-B cells expressed cytotoxic T lymphocyte antigen 4, inducible costimulator, OX40 (CD134), programmed death 1, and TNF-RII, and produced lower concentrations of IL-2 and higher concentrations of IL-10. In a murine model of asthma, an adoptive transfer of Treg-of-B cells before or after immunization sufficiently suppressed Th2 cytokine production and eosinophilic infiltration, and alleviated asthmatic symptoms. B cells isolated from gut-associated lymphoid tissues can generate regulatory T cells that may be important in oral tolerance, and that may be applicable to the alleviation of allergic symptoms.