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.
Graduate Institute of Clinical Medicine, National Taiwan University, No. 7 Chung-Shan South Road, Taipei, Taiwan, Republic of China.
Kuan-Hua
KH
Chu
Bor-Luen
BL
Chiang
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016207:Cytokines