Diabetes is not prevented by Foxp3-transduced CD4+T cells under the IL-12Rβ2 promoter control

Our previous studies have shown that Foxp3 under the control of IFN-γ promoter (IγP-Foxp3) converts pathogenic CD4+Th1 cells into regulatory T cells (Tregs), which control diabetes in non-obese diabetic (NOD) mice. Here, we tested the other hypothesis that transient expression of Foxp3 as controlled by the transient expression of IL-12Rβ2 during Th1 cell derivation is sufficient to convert cells to Tregs. Foxp3, under the control of IL-12Rβ2 promoter (Iβ2P), was lentivirally transduced into naive CD4+T cells from NOD mice. Iβ2P-Foxp3-transduced CD4+T cells could not effectively suppress the incidence of diabetes when transferred into NOD mice. Furthermore, we found that Iβ2P-Foxp3-transduced CD4+T cells, stimulated by a high dose of autoantigen, did not suppress CD4+T cell activation, produce CD4+Foxp3+Tregs, and up-regulate CTLA4 expression. These results suggest that Iβ2P cannot mediate Foxp3 to convert pathogenic CD4+Th1 cells into Tregs which control diabetes in NOD mice.