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CD4+CD25+ regulatory T cells (Treg) have been shown to prevent allergic asthma; however, the role of Treg in airway remodelling resulted from repeated asthmatic episodes is unknown. Increased pulmonary vasculature is seen in airway remodelling and is directly linked to airway hyperresponsiveness (AHR). This study investigated the role of Treg in remodelling angiogenesis by using an ova albumin (OVA) chronic asthma model and OVA-TCR transgenic DO11.10 mice. At chronic phase of the model, airway epithelial and muscle hyperplasia, mucus metaplasia, matrix deposition, increased pulmonary vasculature and AHR were found. When activated DO11.10 Treg were transferred at the chronic stage, leukocyte infiltration by OVA challenge was inhibited and AHR was alleviated. Pulmonary vasculature, but not the epithelial-mesenchymal components, was significantly reduced by Treg transfer (P<0.001). Anti-angiogenesis of Treg was verified by Matrigel plug and Matrigel tube assays; both showed significantly decreased vessel formation at the presence of Treg (P<0.001). Do11.10 Treg secreted IL-10 and TGF-β and inhibited T cell proliferation via cell contacts, suggesting possible anti-angiogenesis mechanism of Treg. This study demonstrates that in addition to suppressing airway inflammation, Treg ameliorate AHR by modulating angiogenesis in airway remodelling, supporting a therapeutic role of Treg in chronic asthma. [ABSTRACT FROM AUTHOR]

Induction of immunological tolerance via anergic or regulatory T cells is a potential therapeutic strategy for immunological diseases such as allergy and autoimmunity. Despite extensive investigation into the mechanism of anergic and regulatory T cell-mediated immune suppression, the exact mechanism is still unclear. This project investigated the migration characteristics of anergic and regulatory T cells, in comparison to conventional T cells, by using a parallel-plate flow chamber assay and ova albumin (OVA)-TCR transgenic DO11.10 mice. Anergic T cells were generated by treating DO11.10 splenocytes with anti-CD80, anti-CD86 and anti-ICOSL blocking Abs before stimulation by OVA. On flowing through ICAM-1 and E-selectin at shear stress of 1.5 dynes/cm², anergic T cells exhibited a significant reduction of adhesion as compared to OVA-stimulated effector T cells (71% reduction, P<0.001). In the same flow chamber system, activated CD4+CD25+ regulatory T cells isolated from DO11.10 mice also showed a significantly decreased adhesion compared to CD4+CD25- T cells (76% reduction, P<0.001). Reduced adhesion of the suppressor cells was also observed when using an endothelial cell-based flow chamber system. These findings demonstrate differential migration phenotypes of suppressor and effector T cells, suggesting distinct migration property may contribute to the execution of individual immune function. [ABSTRACT FROM AUTHOR]