Synergistic Reversal of Type 1 Diabetes in Mice: Evidence of Improved Immune Regulation

This research studied the effects of blocking Interleukin-1 (IL-1beta) in conjunction with an anti-CD3 monoclonal antibody (mAb) on the reversal of diabetes in mice. IL-1beta is a protein that is toxic to beta cells of the pancreas and also involved in the regulation of the immune system. CD3 is a protein required for T-cell activation. T-cells are immune cells that are involved in the destruction of beta cells in the pancreas during the autoimmune process of T1D. Several Phase II trials with anti-CD3 mAbs have shown clinical efficacy. When diabetic mice were treated with a combination of anti-CD3 mAb and an IL-1beta blocker, they showed a more rapid rate of remission of diabetes than mice treated with anti-CD3 alone; the IL1 blocker alone had no effect. Furthermore, the investigators suggested that this combination resulted in long-term tolerance of their immune system. The investigators showed that the combination eliminated certain T-cells and increased the function of Regulatory T-cells involved in immune tolerance.

Reference:

Ablamunits V, Henegariu O, Hansen JB, Opare-Addo L, Preston-Hurlburt P, Santamaria P, Mandrup-Poulsen T, Herold KC. (2012). Synergistic Reversal of Type 1 Diabetes in NOD Mice With Anti-CD3 and Interleukin-1 Blockade: Evidence of Improved Immune Regulation. Diabetes. 2012 Jan;61(1):145-54. Epub 2011 Oct 31.

Ramifications for Individuals with Type 1 Diabetes:

This study supports the idea that combination therapies will be vital for reducing the immune attack that occurs during T1D and resetting the normal balance of the immune system. Because of the dangers of long-term immunosuppressive agents on the immune system, the short-courses of immunotherapies used here that induced long-term effects show promise as a viable approach for human application.

JDRF Involvement:

JDRF funded this study through a Strategic Research Agreement to Dr. Kevan Herold.