Real-time imaging of the pancreas during development of diabetes.

Type 1 diabetes (T1D) is the most common autoimmune disease affecting almost 20 million people worldwide. T1D is thought to be caused by autoaggressive T cells infiltrating pancreatic islets and destroying insulin-producing beta cells. Because insulin therapy, the current treatment for T1D, does not protect against all late complications and because life expectancy is affected, researchers are searching for preventive or curative approaches that block or prevent immune-mediated islet destruction. However, the precise in vivo events that take place in islets during T1D development remain unknown. During the past decade, 2-photon microscopy (2PM) has emerged as a new technique to assess cell-cell interactions in real-time and at high resolution in vivo. This technique has been demonstrated recently to be a promising tool to study the progressive development of T1D pathogenesis at the cellular level. In this review, we propose a new surgical and immunological approach so that 2PM can be utilized to monitor the duration that effector cells reside within an islet, determine the number of effector cells needed for elimination of beta cells, and follow the fate of beta cells when regulatory cells are present. Understanding the cellular dynamics during T1D development is critical for the rational design of immunotherapies.