GAD-IgG-inducing CD4+Foxp3+Treg Cells Suppressing Diabetes Are Involved in the Increasing Ratio of CD80+:CD86+ Cells in NOD Mice

BackgroundOur previous studies have demonstrated that GAD-IgG-transduced splenocytes protect non-obese diabetic (NOD) mice from diabetes by in vitro-inducing CD4+Foxp3+Treg cells. However, the underlying mechanisms by which CD4+Foxp3+Treg cells suppress diabetes remain unclear.MethodsSeven-week-old female NOD mice were intravenously injected with GAD-IgG-transduced splenocytes. The ratio of CD80+:CD86+ cells in splenocytes was analyzed by flow cytometry. The effect of the ratio of CD80+:CD86+ cells on tolerance, diabetes prevention, and Foxp3 expression in GAD-IgG-treated NOD mice was tested by in vitro proliferation, in vivo antibody block, and semi-quantified RT-PCR, respectively.ResultsWe found that the ratio of CD80+:CD86+ cells increased in GAD-IgG-treated NOD mice. After CD4+Treg cells were depleted from GAD-IgG-transduced splenocytes before transfer, the ratio of CD80+:CD86+ cells decreased in NOD mice recipients. The increasing ratio of CD80+:CD86+ cells was positively associated with tolerance, diabetes prevention, and the high level of Foxp3 in GAD-IgG-treated NOD mice.ConclusionsThese findings suggest that the high ratio of CD80+:CD86+ cells is required for the suppressive function of GAD-IgG-inducing CD4+Foxp3+Treg cells in NOD mice.