Influence of CD4 T cell help and Tregs in diabetes induction in RIP‐GP mice

Abstract

Recently, we have developed a virus‐free protocol, which induces Type 1 Diabetes (T1D) in two different RIP‐GP strains with different disease kinetics and incidence. RIP‐GP Arm and RIP‐GP Berlin mice express the glycoprotein (GP) from the lymphocytic choriomeningitis virus (LCMV) strains Armstrong and WE, respectively, under control of the rat insulin promoter resulting in pancreatic LCMV‐GP expression. Our diabetes induction protocol induced T1D in all RIP‐GP Berlin mice seven to twelve days after treatment. In contrast, only maximally 35% of RIP‐GP Arm mice developed transient T1D from day nine onwards. We then analyzed whether LCMV‐specific Smarta CD4 T helper cells would increase diabetes incidence in RIP‐GP Arm mice and whether Smarta CD4 regulatory T cells (Tregs) would decrease T1D incidence in RIP‐GP Berlin mice. Transfer of Smarta T helper cells indeed increased T1D kinetics and incidence in RIP‐GP Arm mice whereas transfer of Smarta Tregs reduced T1D incidence in RIP‐GP Berlin mice to below 30%. In the future, we will analyze the mechanisms of how LCMV‐specific CD4 T helper and Treg cells influence T1D development in the two RIP‐GP strains.