Preclinical Models to Evaluate the Human Response to Autoantigen and Antigen-Specific Immunotherapy in Human Type 1 Diabetes

Type 1 Diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic islet beta-cells by auto-reactive T cells. The clinical management of T1D faces the lack of fully predictive biomarkers in its preclinical stage and of antigen-specific therapies to induce or re-induce immune tolerance to beta-cell autoantigens and prevent its development. From a therapeutic standpoint, preclinical models of T1D have fallen short of directly translating into humans. To circumvent this limitation, preclinical models are being optimized to allow defining autoantigen epitopes that are presented to T cells and directly apply to the human. In this review, we propose to make a point on the latest available models such as humanized immunodeficient NOD mice models and HLA and autoantigen transgenic mice and their application in the context of T1D.