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

Abstract

Mechanisms of autoimmunity are varied and complex, resulting from the failure of multiple layers of immune tolerance mechanisms. Failures occur in the thymus and bone marrow during lymphocyte development, in the secondary lymphoid organs during activation, and finally at the site of autoimmunity. We will discuss mechanistic insights into autoimmune processes in the periphery. The diverse nature of the cellular composition, milieu, and structure of the target tissue introduces the potential for differing mechanisms of activation and tolerance that are environmentally dependent. Live imaging in autoimmunity provides the ability to analyze immune cell dynamics within the complex environment where disease occurs, including immune cell interactions with each other and the tissue. In depth research imaging the secondary lymphoid organs and tissue target sites, particularly in models of multiple sclerosis (MS) and type 1 diabetes (T1D), have revealed mechanisms of T cell activation and tolerance, immune cell trafficking to the autoimmune disease site, and immune cell function and regulation at the autoimmune site. Preservation of the intact tissue for imaging has been key to many of the findings that resulted from these studies. These findings have informed our knowledge of T cell activation, regulation, and function which is relevant to health, tumors, and autoimmunity.