Regulatory T Cells Induced by Mucosal B Cells Alleviate Allergic Airway Hypersensitivity
Date Issued
2012
Date
2012
Author(s)
Chu, Kuan-Hua
Abstract
Asthma is one of the most common chronic airway inflammatory diseases. Induction of immunologic tolerance via mucosa has been used for treating allergic diseases. B cells, the major cell population in Peyer’s patches, have been shown to induce the development of Treg cells. This study aimed to investigate the role of B cells in Peyer’s patches to tolerance induction and on Treg cell functions. In vitro suppressive assay and ELISA were used to evaluate the function of T cells stimulated by Peyer’s patches B cells (Treg-of-B(P) cells). The therapeutic potential of Treg-of-B(P) cells on ovalbumin (OVA)-induced murine asthma is evaluated by measuring OVA-specific IgE, Th2 cytokine production, eosinophilia in Bronchoalveolar lavage fluid (BALF) and histopathological analysis.
First, we demonstrated that oral fed mice with OVA 0.5 mg for five days could diminish Th2 responses in BALF. High dose antigen administration (20mg) results in decreased CD4 T cell number, in contrast, low dose antigen helped Foxp3+ or IL-10 producing T cells induction. In vitro assay showed that Treg-of-B cells were found to exert suppressive function on T cell proliferation. Antigen-loaded B cells isolated from Peyer’s patches were more tolerogenic, compared with splenic B cells, and had the potential to generate more suppressive Treg-of-B cells via IL-10 production and cell-cell contract. Treg-of-B cells expressed CTLA4, ICOS, OX40, PD-1, and TNFRII and produced lower IL-2 and higher IL-10. Blocking experiment shows that IL-10, GITR and PD-1 mediate the suppressive effect of Treg-of-B(P) cells. Furthermore, we identify that FOB and MZB cells are capable of Treg cells generation. In addition, Peyer’s patches B cells are much better than Peyer’s patches DCs on generating Treg cells. In the murine model of asthma, an adoptive transfer of Treg-of-B(P) cells pre- or post- immunization could sufficiently suppress Th2 cytokine production and eosinophil infiltration, and alleviate asthmatic symptoms.
B cells isolated from gut-associated lymphoid tissues, GALT, can generate regulatory T cells that may be important in oral tolerance and be applicable for alleviating allergic symptoms.
Subjects
mucosal tolerance
Peyer’s patches
B cells
asthma
regulatory T cells
airway hyperresponsiveness
Type
thesis
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