While we have learned a great deal about the immune cells involved in type 1 diabetes (T1D) by studying blood of patients, a major challenge is that the actual cells involved in injury to the pancreas are not in the blood where they are relatively easy to detect and study. It is not at all clear how cells in the blood relate to those that actually associated with the pancreas. Also hidden from us are the cells that move between the pancreas, the blood and other tissues of the immune system. Here, we will leverage major existing strengths at Penn including access to unique samples to study immune cells in T1D and healthy controls in three different compartments. These include not only the blood, but also immune cells from the pancreas of patients affected by T1D obtained through the Human Pancreas Analysis Program at Penn, as well as immune cells in the entirely unexplored lymphatic compartment which we obtain through an innovative procedure developed at Penn. We will also obtain blood and lymphatic immune cells from patients with multiple sclerosis (MS) as well as their spinal fluid, and interrogate them in the identical fashion, so we can compare the cell profiles in the 3 compartments and learn not only about previously unexplored roles and relationships of immune cells in T1D, but also of similarities and differences that may exist between patients with T1D and MS. Ultimately we hope we will identify measurements in the blood that better correspond with what is actually happening in tissue being injured so we can more effectively and safely target them therapeutically.