We now report further long-term in vivo studies showing that two of our most promising CD40–CD40L SMIPPIs, DRI-C21041 and DRI-C21095, were able to • significantly prolong the survival of islet allografts in two mouse models of islet transplantation in different sites and • prevent the onset of autoimmune diabetes in the non-obese diabetic (NOD) mouse model of T1D. Here, CD40 is linked to type 1 diabetes mellitus.