Mechanisms Mediating Anti-CD3 Antibody Efficacy
Insights from a Mathematical Model of Type 1 Diabetes
Abstract
Abstract: Anti-CD3 antibody therapy, a promising clinical approach for the treatment of type 1 diabetes (T1D), was investigated using a mathematical model of T1D in the female nonobese diabetic (NOD) mouse. Analyses of model simulation results indicate that, in addition to the known direct effects of anti-CD3 antibody on T lymphocytes, two additional mechanisms are required for sustained disease remission: (a) rapid regrowth of healthy β cells following clearance of islet inflammation and (b) enhanced regulatory T cell activity and/or phenotypic changes in antigen presenting cells (APCs) that promote a stable regulatory environment in the pancreas.