We showed that ppins antigens excluded from expression in the endoplasmic reticulum (ER) did not induce CD8<sup>+</sup> T cells or autoimmune diabetes in RIP-B7.1 tg mice, but efficiently suppressed spontaneous diabetes development in NOD mice as well as ppins-induced CD8<sup>+</sup> T cell-mediated autoimmune diabetes in <i>PD-L1</i><sup>-/-</sup> mice.
HLA-DR3-DQ2<sup>+</sup>huCD4<sup>+</sup>IA/IE<sup>-/-</sup>RIP.B7.1<sup>+</sup> mice spontaneously developed autoimmune diabetes (incidence 46% by 35 weeks of age), accompanied by numerous hallmarks of human type 1 diabetes (autoantibodies against GAD65 and proinsulin; pancreatic islet infiltration by CD4<sup>+</sup>, CD8<sup>+</sup> B220<sup>+</sup>, CD11b<sup>+</sup> and CD11c<sup>+</sup> immune cells).
Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model.