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.

Peptide-pulsed immature dendritic cells reduce response to beta cell target antigens and protect NOD recipients from type I diabetes.

Our previous work demonstrated peptide-pulsed mature myeloid dendritic cells (DC) presenting beta cell antigens induce tolerance. Here we determine whether immature DC (iDC) presenting dominant (insulin beta9-23 chain, proinsulin C19-A3) or ignored (glutamic acid decarboxylase 65(78-97)) antigen determinants promote tolerance. Nonobese diabetic (NOD) mice were given injections of either unpulsed or peptide-pulsed myeloid iDC beginning at 9 weeks of age for 3 consecutive weeks.

Heightened interferon-alpha/beta response causes myeloid cell dysfunction and promotes T1D pathogenesis in NOD mice.

Increasing attention is drawn to the contributions of abnormalities in both innate and acquired immune responses to the pathogenesis of autoimmune diseases, such as type 1 diabetes (T1D). Dendritic cells (DC) are critical immune cells linking innate and acquired immune responses and previous studies in NOD mice suggest abnormalities in these cells. To address DC dysregulation we examined kinetic global gene expression in NOD and B6 GM-CSF/IL-4-induced bone marrow-derived DC following lipopolysaccharide (LPS)-stimulation.