Antigen presenting cells play a critical role in determining response to regulatory T cell therapy in type 1 diabetes

Abstract

Type 1 diabetes (T1D) is an autoimmune disease in which the immune system attacks pancreatic beta cells, leading to high blood glucose levels and requiring lifelong insulin therapy. There is no cure, and individuals with T1D may face a reduced lifespan of up to 12 years. Defects in regulatory T cells (Tregs) are a key contributor to disease onset and are being explored as a therapeutic avenue. However, the effectiveness of Treg therapy remains uncertain. Research is further limited by the inability to directly observe pancreatic and lymph node activity during the long presymptomatic stage of T1D. In this study, we develop a mathematical model for beta and T cell dynamics. We find both Treg quality and quantity affect disease progression, and that antigen-presenting cell (APC) dynamics play a central role. Notably, Treg therapy combined with APC depletion improves outcomes, especially with strong peptide-induced APC activation.