Study of the mechanism of oral tolerance in a transgenic murine model of asthma
Date Issued
2006
Date
2006
Author(s)
Chen, Chien-Chang
DOI
en-US
Abstract
Oral administration of antigens can induce immune tolerance to specific antigens and this characteristic phenomenon might be used as a potential treatment for allergic diseases, such as asthma. Recent researches have shown that oral tolerance induced by continuous feeding of ovalbumin (OVA) in the murine model can result in the activation of regulatory T cells and/or deletion of antigen-specific T cells. However, the underlying mechanisms are yet to be clarified. Therefore, we would like to study further the functional change of antigen-specific T cells after oral tolerance induction. We use OVA-T-cell receptor (OVA-TCR) transgenic mice on the BALB/c background, which recognizes the 323-339 peptide fragment of OVA, as model animal.
First, we established an animal model with airway hyperresponsiveness, antigen specific IgE production and eosinophilia in OVA-TCR transgenic mice. In this study, oral tolerance was induced by feeding different dose of OVA, and then examined the number and function of OVA-specific T cells. The results showed that oral tolerance induced by both high-dose and low-dose of OVA could suppress the reactivity of asthma, such as the reduction of Th2-cytokine (IL-4, IL-5) secretion, decreased airway hyperresponsiveness, reduced eosinophila, and increase regulatory cytokine (TGF-β and IL-10) secretion. Furthermore, the numbers of OVA-specific T cell were increased in the group with high-dose oral tolerance. Taken together, these findings indicate that oral tolerance induced by feeding low-dose of antigen generates TGF-β-secreting T cells, and that high-dose oral tolerance can be achieved by angeric antigen-specific T cells. Although much more studies are needed, these results suggest that TGF-β may play a crucial role in the induction of oral tolerance.
Subjects
口服耐受性
基因轉殖小鼠
氣喘
Oral tolerance
Transgenic mice
Asthma
Transforming growth factor-beta
Type
other
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