Autoimmunity in motion: Mechanisms of immune regulation and destruction revealed by in vivo imaging*

Abstract Autoimmunity arises when mechanisms of immune tolerance fail. Here we discuss mechanisms of T cell activation and tolerance and the dynamics of the autoimmune response at the site of disease. Live imaging of autoimmunity provides the ability to analyze immune cell dynamics at the single‐cell level within the complex intact environment where disease occurs. These analyses have revealed mechanisms of T cell activation and tolerance in the lymph nodes, mechanisms of T cell entry into sites of autoimmune disease, and mechanisms leading to pathogenesis or protection in the autoimmune lesions. The overarching conclusions point to stable versus transient T cell antigen presenting cell interactions dictating the balance between T cell activation and tolerance, and T cell restimulation as a driver of pathogenesis at the site of autoimmunity. Findings from models of multiple sclerosis and type 1 diabetes are highlighted, however, the results have implications for basic mechanisms of T cell regulation during immune responses, tumor immunity, and autoimmunity.