Interleukin-2 and type 1 diabetes: new therapeutic perspectives

A new sort of CD4+T cells, so-called regulatory T cells (Tregs), has been described in 1996. Tregs are suggested to have an important function consisting in controlling autoimmune reactions. In humans, absence of Tregs induces the IPEX syndrome characterized by the presence of several autoimmune diseases. These cells depend on interleukin-2 (IL-2) for proliferating and controlling the T effector cells (Teff) reaction, but they do not have the capacity to produce IL-2. In type 1 diabetes (T1DM), a hypothesis is that a lack of IL-2 in pancreas could prevent Tregs action and lead to beta cells destruction. In NOD mice, low dose IL-2 treatment at the initial time of diabetes can rescue insulin secretion by restoring proteins expression that are necessary for Tregs regulatory function in the pancreas. Using low doses instead of high doses IL-2 prevents Teff activation which also depends on IL-2. These results led to conduct a dose-effect trial in human T1DM. This trial aimed at determining the therapeutic condition, which induces Tregs activation without major side effects, in a therapeutic perspective to recover insulin secretion at the apparition of diabetes.