Effects Of Regulatory T Cells And Notch Signal On Dendritic Cells On Th1/Th2 Paradigm In Asthmatic Mice

Asthma is characterized by chronic allergic inflammation of the airways, eosinophils, macrophages, and mast cells. A critical role in the pathophysiology of asthma has been attributed to the excess activation of T lymphocytes and production of helper 2 lymphocytes (Th) that promote IgE production and eosinophil activation by release of cytokines, such as interleukin (IL)-4, IL-5, and IL-13. The pathogenesis of asthma has been regarded as the imbalance between Th1 and Th2 cells, which is now considered as superficies. In fact, the reason for the activation and proliferation of CD4+ T cells and differentiation towards Th2 cells is the dysfunction of immune tolerance in patients with asthma.Regulatory T cells (Treg) play an important role in the induction and maintenance of peripheral tolerance, but it is not clearly known whether there exit deficiency of polarization and defects in immunoregulation of Treg cells. Dendritic cells (DCs) control the ongoing asthmatic inflammation by means of induction of both tolerogenic as well as immune responses decided by the biological characters of DCs, and the induced Treg polarization is influenced by the antigen presentation and nature of the costimulatory signal molecule on DCs. However, the mechanisms in the preferential induction of naive T cells by DCs into Treg cells rather than memory T cells remain unknown. It has been found that a signaling pathway controlled by Notch1/Serrate1 contributes to the peripheral CD4~+T cells to become Treg. Up to now, the effects and mechanisms of the signaling pathway on the dysfunction of immune tolerance in asthma have not been reported.In this study, we observed the changes in the count of CD4~+CD25~+T cells, the expression of inhibitory cytokines and the costimulatory molecules, and the airway inflammation in the asthmatic and anti-CD25 McAb treated mice. The effects of asthmatic and normal CD4~+CD25~+T cells on the proliferation and production of the Th1/Th2 cytokines of CD4~+ T cells were also examined. We constitutively expressed Serrate1 on DCs, which is the ligand of Notch1, and investigated the DC phenotype and the functional consequences in the regulation of the differentiation of asthmatic CD4~+CD25~+T cells and...