CD4+CD25+ Regulatory T Cells Decreased CD8+IL-4+Cells in a Mouse Model of Allergic Asthma
the interplay between regulatory T cells and CD8 cells in a mouse asthma model
Interleukin (IL)-4-producing-CD8 (cytotoxic T cells, Tc) contribute to lung eosinophilia and airway hyper-responsiveness (AHR) to an antigen. CD4+CD25+ regulatory T cells (Tregs) attenuate airway inflammation and AHR. This study investigated whether Tregs decrease Tc2frequencies in ovalbumin (OVA)-induced asthma model of mice. Female C57BL/6 mice were sensitized with OVA intraperitoneally and challenged with OVA intranasally to induce allergic asthma model. Tregs were sorted by fluorescence activated cell sorting (FACS) and magnetic activated cell sorting (MACS) microbeads. OVA-sensitized mice were injected with Tregs or phosphate buffer saline (PBS) by tail vein ahead of the first challenge. Airway inflammation and airway hyper-responsiveness (AHR)were evaluated by histological analysis and invasive method, respectively. OVA-specific IgE and cytokine levels were detected by ELISA. Flow cytometry was used to detect the percentages of Tc1 and Tc2. Gata3 and T-bet mRNA was determined by quantitative PCR (qPCR). OVA-sensitized and challenged mice displayed typical asthma features, which included eosinophilic airway inflammation, higher levels of Th2 cytokines and AHR. Gata3 mRNA, Tc2 frequencies and OVA-specific IgE levels were significantly increased in OVA-sensitized and challenged mice. Compared to PBS treatment, Tregs decreased Tc2 frequencies, airway inflammation, Th2 cytokine levels and AHR in OVA-sensitized and challenged mice. IL-13 levels were negatively correlated with Tc1 frequencies and with IFNg levels in experimental mice. Our results demonstrated that Tregs could prevent airway inflammation and AHR by decreasing Tc2 frequencies and cytokine levels in OVA-induced asthma model of mice, supporting Tregmight be as a potent therapeutic target for alleviating airway inflammation and AHR.
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