Combination Anti-CD4 and Anti-CD8 Therapy Caused T1D Remission in Mice

T1D is marked by the progressive infiltration of pancreatic islets by destructive cells of the immune system and the subsequent destruction of the beta cells. At the time of a T1D diagnosis, it is estimated that 80–90% of pancreatic beta cells have been destroyed by the immune system. However, the remaining 10-20% of beta cells could form the foundation of a strategy to reverse T1D if the autoimmune attack could be suppressed at the time of diagnosis. Destructive or killer T-cells are the primary immune system controllers of beta cell destruction in T1D. These cells outweigh the effects of their non-destructive counterparts known as T regulatory cells or T-regs, thereby precipitating disease. In this mouse study, the authors tested whether a combination of antibodies called anti-CD4 and anti-CD8 could stop the deleterious function of the destructive T-cells, elicit remission and establish long-term beta cell survival and function in recent-onset diabetic mice. Study results showed that remission occurred, was immediate, and long lived; 18 out of 19 of the mice remained diabetes-free 200 days after antibody treatment. Using imagining techniques, the authors also found that 60% of the islets were free of T-cell infiltration. This effect was specific to the pancreas, leaving other parts of the immune system unaffected. These studies show that incapacitating destructive T-cells by inhibiting two molecules on the surface of these cells can effectively reverse new onset disease in this mouse model of T1D.

Ramifications for Individuals with T1D:

These findings demonstrate the potential impact of targeting and disabling key components on certain immune cells specific for beta cell destruction. If initiated at the onset of clinical diabetes in humans, this may be a robust approach to ensure long term survival and function of the remaining beta cells in the pancreas. Such a therapeutic approach might halt or slow further progression of disease or ideally even potentially reverse it.

JDRF Involvement:

This work was funded in part by JDRF.

Investigators and Institutions:

This work was led by Dr. Roland Tisch at the University of North Carolina, Chapel Hill.

Reference:

Zuoan Yi, Ramiro Diz, Aaron J. Martin, Yves Maurice Morillon, Douglas E. Kline, Li Li, Bo Wang, and Roland Tisch (2012) Long-Term Remission of Diabetes in NOD Mice Is Induced by Nondepleting Anti-CD4 and Anti-CD8 Antibodies. Diabetes 61:2871-2880.