Visualizing the Attack of Killer T-Cells in Diabetic Mice

The mechanisms by which Killer T-cells destroy the beta cells of the pancreas during the autoimmune attack that occurs with T1D remain largely unknown. In the present study, the investigators use live imaging of mice with T1D to visualize the behavior of Killer T-cells in the pancreas. The goal of these studies was to track Killer T-cells after activation within the immune system to the point of the onset of clinical high blood glucose levels. The authors show that after Killer T-cells encounter antigen within the islets of the pancreas, a subset of these cells would subsequently kill beta cells at a relatively slow rate. Furthermore, the investigators show that this process by which Killer T-cells encounter beta cells is likely a random process rather than a result of specific, directed attack.

Reference:

Coppieters K, Amirian N, von Herrath M. (2012). Intravital imaging of CTLs killing islet cells in diabetic mice. J Clin Invest. Jan 3;122(1):119-31. doi: 10.1172/JCI59285. Epub 2011 Dec 1.

Ramifications for Individuals with Type 1 Diabetes:

This study suggests that Killer T-cells involved in the autoimmune attack leave blood vessels and enter the pancreas, where the Killer T-cells then randomly encounter antigen on the beta cells. This interaction may ultimately result in the destruction of beta cells, resulting in the onset of clinical hyperglycemia and T1D. Therefore, therapeutic strategies aimed at preventing Killer T-cells from exiting blood vessels in susceptible or resent-onset individuals may be an attractive therapeutic approach.

JDRF Involvement:

JDRF funded Dr. von Herrath through a Scholar Award for these studies.