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

Our previous study has demonstrated that transfusion of UVB-irradiation-induced apoptotic beta cells effectively prevents type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. However, the limitation of beta 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-beta cells to prevent T1D. We find that apoptotic splenic stromal cells significantly suppress beta cell antigen-reactive T cell proliferation in vitro and in vivo. Moreover, beta cell antigen-specific T cells primed by beta cell antigens in the presence of apoptotic stromal cells have markedly reduced responsiveness to the re-stimulation of the same beta cell antigen. We also find that beta 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 beta 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 beta cell antigens. This study provides an effective and convenient approach for managing T1D by utilizing apoptotic non-beta cells.