Infusion of UVB-treated splenic stromal cells induces suppression of β cell antigen-specific T cell responses in NOD mice

Our previous study has demonstrated that transfusion of UVB-irradiation-induced apoptotic β cells effectively prevents type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. However, the limitation of β cell source would preclude the clinical application of this approach. Therefore, in the present study, we have attempted to establish a more practical approach by utilizing apoptotic non-β cells to prevent T1D. We find that apoptotic splenic stromal cells significantly suppress β cell antigen-reactive T cell proliferation in vitro and in vivo. Moreover, β cell antigen-specific T cells primed by β cell antigens in the presence of apoptotic stromal cells have markedly reduced responsiveness to the re-stimulation of the same β cell antigen. We also find that β cell antigen-specific IL-10-producing CD4+ T cells are induced in the presence of apoptotic splenic stromal cells. As expected, transfusion of apoptotic stromal cells effectively protected NOD mice from developing T1D. Furthermore, the proliferation of adoptively transferred β cell antigen-specific TCR-transgenic T cells in pancreatic draining lymph nodes is markedly suppressed in UVB-stroma-treated mice, indicating that UVB-stroma treatment induces immune tolerance to multiple β cell antigens. This study provides an effective and convenient approach for managing T1D by utilizing apoptotic non-β cells.