Previous work has indicated that type 1 diabetes (T1D) pathology is highly driven by reactive oxygen species (ROS). One way in which ROS shape the autoimmune response demonstrated in T1D is by promoting CD4+ T cell activation and differentiation. As CD4+ T cells are a significant contributor to pancreatic β cell destruction in T1D, understanding how ROS impact their development, activation, and differentiation is critical. Recent Advances: CD4+ T cells themselves generate ROS via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and electron transport chain activity. Moreover, T cells can also be exposed to exogenous ROS generated by other immune cells (e.g., macrophages and dendritic cells) and β cells. Genetically modified animals and ROS inhibitors have demonstrated that ROS blockade during activation results in CD4+ T cell hyporesponsiveness and reduced diabetes incidence. Critical Issues and Future Directions: Although the majority of studies with regard to T1D and CD4+ T cells have been done to examine the influence of redox on CD4+ T cell activation, this is not the only circumstance in which a T cell can be impacted by redox. ROS and redox have also been shown to play roles in CD4+ T cell-related tolerogenic mechanisms, including thymic selection and regulatory T cell-mediated suppression. However, the effect of these mechanisms with respect to T1D pathogenesis remains elusive. Therefore, pursuing these avenues may provide valuable insight into the global role of ROS and redox in autoreactive CD4+ T cell formation and function.
Keywords: CD4+ T cells; ROS; regulatory T cells; type 1 diabetes.