Status of autoimmune diabetes 20-year after generation of BDC2.5-TCR transgenic non-obese diabetic mouse

Abstract

Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of insulin-producing β cells by autoreactive T cells, leading to lifelong dependency on insulin therapy and increased risk of long-term cardiovascular complications. Here we take the opportunity of the 20^th anniversary of the generation of the BDC2.5 TCR transgenic non-obese diabetic (NOD) mouse model, to provide a brief overview of the significant progress that has been made in understanding the role of T cells in the disease pathogenesis period. This included development of hundreds of reagents that block or even reverse new-onset disease by directly or indirectly controlling T cells. We also reflect on the sobering fact that none of these strategies has shown significant efficacy in clinical trials and discuss potential reasons hindering translation of the preclinical findings into successful therapeutic strategies and potential ways forward.

Keywords: Autoimmune diabetes; Immunotherapy; T cells; BDC2.5 T cells; Anti-CD3; Immunosuppression

Core tip: Our understanding of type 1 diabetes pathogenesis has significantly improved over the last three decades. We went from not knowing very little to acquisition of significant details about the role of the immune system and different T cell subsets in the disease process. The non-obese diabetic mouse model contributed and continues to contribute to our understanding of the disease process. This article pays tributes to the major role T-cells bearing-cell-specific T-cell receptors transgenic mouse played in shaping of our understanding of the disease process. We also divulge to briefly discuss current challenges facing development of a safe immunotherapy for the disease.