Tracking the Recruitment of Diabetogenic CD8⁺ T-Cells to the Pancreas in Real Time

Abstract

Development of autoimmune diabetes in both humans and mice is preceded by a prolonged period of inflammation of pancreatic islets by autoreactive T-cells. Noninvasive imaging techniques, including positron-emission tomography and optical or magnetic resonance imaging, have been used to track the recruitment of lymphocytes to sites of inflammation. These techniques, however, rely on labeling strategies that are non–antigen specific and do not allow specific tracking of the recruitment of autoreactive lymphocytes. Here we describe an antigen-specific magnetic label to selectively target a prevalent population of diabetogenic CD8⁺ T-cells that contribute to the progression of insulitis to overt diabetes in NOD mice. Superparamagnetic nanoparticles coated with multiple copies of a high-avidity peptide/major histocompatibility complex ligand of these T-cells (NRP-V7/K^d) are endocytosed by CD8⁺ T-cells in an antigen-specific manner. Using these T-cells as probes, we show that inflammation of pancreatic islets by autoreactive T-cells can be detected in real time by magnetic resonance imaging. This study demonstrates the feasibility of visualizing the presence of ongoing autoimmune responses noninvasively.