Gustaf Christoffersson

My current research projects are focused on understanding how the autoreactive immune response during onset of type 1 diabetes is regulated. I’m interested in what triggers the specific immune response in the pancreas, and how that response can be curbed by our own immune system.

The mechanisms behind the massive infiltration of T-lymphocytes into the pancreas that is seen in experimental diabetes and in tissue samples from patients with type 1 diabetes are not completely clear. Conflicting data exist regarding the population of T-lymphocytes in the afflicted pancreas, their reactivity towards islet-specific antigen, and whether this is a cell intrinsic or –extrinsic effect. To study this, we are using advanced intravital multiphoton imaging of the mouse pancreas during onset of diabetes. Instead of getting snapshots of the disease progress as one gets with traditional methods, imaging the dynamics at the epicenter of the disease gives new insights into the mechanisms of diabetes onset. This approach enables us to follow cell movement from the bloodstream to the organ - from the organ to the lymphatics. This also allows the study of more rare and dynamic events in the pancreas, such as looking at whether T-lymphocyte-receptor specificity is required for direct lymphocyte beta-cell toxicity, and how immune cells of different subsets interact before the attack on the insulin producing cells.

Knowing this chain of events in detail and identifying the players involved gives us the opportunity to interfere at different steps to halt diabetes onset or to treat manifest disease. In all our research, we keep close contact with the clinical situation, and by so we for example interrogate the validity of our preclinical findings in epidemiological studies.

'The hornet's nest of type 1 diabetes'. This confocal microscopy image from a diabetic mouse shows the vast infiltration of immune cells (here macrophages and T cells) into the pancreatic islets which harbor the insulin-producing beta cells.

For further information about this research project please contact Gustaf Christoffersson