Study on the Immune Regulatory Mechanisms of Single Allergen-Induced Oral Tolerance Inhibits Airway Inflammation in Conjugated Allergen Immunized Mice
Date Issued
2015
Date
2015
Author(s)
Chien, Chien-Hui
Abstract
Although oral tolerance has been considered the result of a number of protective mechanisms, the real mechanisms of oral tolerance are yet to be defined. The present study was aimed to determine whether a single allergen-induced oral tolerance would affect the immune responses to other related allergens that were primed together with the orally treated allergen. We investigated whether oral administration of a single antigen would protect the conjugated antigen-sensitized mice from the other antigen induced airway inflammation. We found that oral administration of ovalbumin (OVA) was able to prevent the immune responses to β-lactoglobulin (BLG) in BLG-conjugated OVA (B-O) sensitized mice and vice versa. Oral administration of antigen enhanced the suppressive potential of CD4+CD25+ T cells to inhibit non-antigen-specific T cell proliferation. The B cell-induced regulatory T (referred to as Treg-of-B) cells showed several similarities with orally treated CD4+CD25+ T cells, including the expression of inducible T-cell co-stimulator (ICOS) and programmed cell death 1 (PD1), the production of interleukin (IL)-10 and transforming growth factor (TGF)-β, and the non-antigen-specific suppressive ability, and therefore might play a role in the sophisticated mechanism of oral tolerance. The results suggested that single allergen induced oral tolerance had the ability to modulate the immune responses to other related allergens and was able to be more clearly detected in our conjugated antigen-induced asthmatic model. In addition, we investigated the effect of re-encounter the antigen-presenting B cells on the generation of Treg-of-B cells. We found that the IL-10-producing population and production of IL-10 increased in Treg-of-B3rd cells. IL-10 also played a role in the suppressive function of Treg-of-B3rd cells. Treg-of-B3rd cells maintained expressions of ICOS, PD1, and cytotoxic T-lymphocyte associated antigen 4 (CTLA4) and the suppressive abilities as that of Treg-of-B1st cells. The major population of IL-10-producing Treg-of-B3rd cells was confined to the avian musculo-aponeurotic fibrosarcoma oncogene homolog (c-Maf)-expressing population. The levels of IL-10, IL-4, IL-27, and TGF-β increased gradually during the generation of Treg-of-B3rd cells. These results suggested that re-encounter the antigen-presenting B cells converted CD4+CD25- T cells into IL-10-producing Treg-of-B3rd cells and the pathway of IL-27/TGF-β-c-Maf might be involved. In summary, our results suggested that Treg-of-B cells had a non-antigen-specific suppressive function and might play a role in the sophisticated mechanism of oral tolerance. Moreover, re-encounter the antigen-presenting B cells induced IL-10-producing CD4+ Treg-of-B3rd cells via activation of c-Maf. In the future, the upstream signaling activated generation of IL-10-producing Treg-of-B cells, the relationship between c-Maf and the suppressive function of Treg-of-B cells required further research and the binding proteins of c-Maf in the regulation of IL-10 or other genes required more investigations as well.
Subjects
Oral tolerance
regulatory T cells
airway inflammation
allergic asthma
IL-10-producing T cells
c-Maf
Type
thesis
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