SAT102 Natural History Of Type 1 Diabetes In Humanized Mouse Model

Abstract

Abstract Disclosure: A. Aldasouqi: None. S. Rafiqi: None. J.C. Jaume: None. S. Imam: None. Type 1 diabetes (T1D) is an autoimmune disease caused by an imbalance in T-regulatory and T-effector cells characterized by the destruction of insulin-producing beta cells by T-effector cells, leading to insulin deficiency and complexities like diabetic nephropathy, retinopathy, and neuropathy. Researchers at The University of Toledo have developed a humanized mice model which spontaneously develops T1D at 3-5 weeks of age and mimics human T1D. This study aims to monitor blood glucose levels before the onset of T1D (preweaning stage mice) and track the dynamics of immune cells using flow cytometry throughout the progression of the disease. Our results show that T-regulatory cells constitute 4.773% ± 0.81% cells at preweaning which drops to 2.60± 0.35 (%) in males and 1.78 ± 0.58 (%) in females at the 10th week while CD8+ T cells producing interferon-gamma (cytotoxic lymphocytes, CTLs) constitute 3.32 ± 0.60 (%) at preweaning, which increased to 27.625± 1.43 (%) in males and 21.13± 2.87 (%) in females as the disease progresses. This reduction in T-regulatory cells and enrichment of CD8s and CTLs leads to the destruction of beta cells as seen in humans as well. Dysregulation of immune responses can be correlated with the progression of diabetes in terms of blood glucose levels which increased from 147mg/dl (preweaning), peaked to 373mg/dl in 5th week, and was observed in partial remission stage around the 8th week as observed in human T1D ‘honeymoon period’. This study will help us to understand the immune dynamics in the progression of T1D as it helps us to present a better picture of the status of immune cells in a human-like immune system and provides benchmark data of the interplay of the immune system. Presentation: Saturday, June 17, 2023