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

Abstract

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 antigenspecific 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.

Concise Review: Mechanisms Behind Apoptotic Cell-Based Therapies Against Transplant Rejection and Graft versus Host Disease

“…The discovery that, under certain conditions, cells undergoing apoptosis down‐regulate the proinflammatory/proimmunogenic properties of APCs, plus the fact that apoptotic cells are a natural source of foreign or autologous Ags for APCs, led to the idea of testing apoptotic cell‐based therapies for induction of Ag‐specific immuno‐suppression in T cell‐mediated disorders in the fields of transplantation and autoimmunity .…”

Allogeneic intra-bone marrow transplantation prevents rheumatoidarthritis in SKG/Jcl mice

“…However, we submit that IBM-BMT will become a powerful strategy for treating intractable autoimmune diseases of patients. Finally, we note a recent symposium on this and related issues of bone marrow and mesenchymal stem cell transplantation [43][44][45][46][47][48][49][50][51][52][53].…”

Steady-State Cell Apoptosis and Immune Tolerance - Induction of Tolerance Using Apoptotic Cells in Type 1 Diabetes and Other Immune-Mediated Disorders

“…Intravenous infusion of apoptotic cells can significantly prevent type 1 diabetes in non-obese diabetic mice (101)(102)(103). More specifically, weekly delivery of ECP-treated spleen cells significantly delayed the onset of diabetes.…”