Mechanisms of regulatory T-cell induction by antigen-IgG-transduced splenocytes

Abstract

Our previous studies have demonstrated that splenocytes, transduced with glutamate decarboxylate 65 (GAD) and IgG fusion construct, protect non-obese diabetes (NOD) mice from diabetes. However, the mechanism by which this strategy prevents diabetes is not well understood. Here, we found that CD4(+)Foxp3(+)Treg cells, in vitro induced by GAD-IgG-transduced splenocytes, after transfer, were responsible for prevention of diabetes in NOD mice. Further studies suggested that GAD-IgG-transduced B cells could secrete high level of TGF-beta and stimulated CD4(+)T cells to secrete high level of IFN-gamma. Finally, we found that when TGF-beta and/or IFN-gamma were blocked, CD4(+)Foxp3(-)T cells were not converted into CD4(+)Foxp3(+)Treg cells. The results suggest that GAD-IgG-transduced B cells via TGF-beta and IFN-gamma in vitro induce the CD4(+)Foxp3(+)Treg cells which are responsible for prevention of diabetes in NOD mice by GAD-IgG-gene transfer.