Type 1 diabetes (T1D) is caused by the autoimmune mediated destruction of the pancreatic islet β cells, leading eventually to absolute deficiency in insulin. The development of autoimmunity precedes the clinical diagnosis of diabetes and is due in large part to the inability of regulatory T cells (Tregs) to control the pathogenic autoreactive T cells from destroying the insulin-producing  pancreatic islet β cells.

In clinical trials, less than 30% of patients T1D achieve glycaemic targets while in standard clinical practice rates are usually less than 16%. Importantly, at the time of diagnosis of T1D, there are  residual β cells capable of producing insulin.  Remission of the autoimmunity at this stage could have significant therapeutic benefit. Preservation of β-cell function has the potential to improve metabolic control more effectively, at lower cost and with higher patient acceptability than current standard insulin replacement therapy. 

The DIABIL-2 project aims to stimulate Tregs by ultra-low dose interleukin-2 (IL-2) at diagnosis of T1D to prevent further autoimmune-mediated destruction of β-cells. This will prevent or delay T1D disease progression and could improve clinical outcome for patients.

About Type 1 Diabetes (T1D)
T1D is one of the most common severe chronic autoimmune diseases worldwide. In Europe its incidence is rapidly rising in children, with a predicted 70% increase in cases over the next 15 years. The age at T1D diagnosis is decreasing, with a predicted doubling of cases in children under the age of 5 years in the same period. The cause of T1D is the autoimmune-mediated progressive destruction of insulin-producing pancreatic β cells leading to insulin deficiency and hyperglycaemia.



A Model for the Pathogenesis of Type 1 Diabetes Based on Genetic Etiological Studies in Humans
(From J.A. Todd, Etiology of Type 1 Diabetes, Immunity, 2010)


The IL-2 pathway is central to the development of T1D. Tregs are dependent on IL-2. Treatment with IL-2 should improve Treg function and prevent effector CD4 and CD8 T cells killing of β-cells and resulting destructive inflammation.



About Treg cells and Interleukin-2
Regulatory T cells (Tregs) form a subpopulation of T lymphocytes that regulate the immune system to maintain tolerance to self-antigens and prevent autoimmune diseases. As T1D is caused by the failure of Tregs to block autoimmune destruction of pancreatic ß-cells, Treg stimulation has the potential to stop the process, preserve ß cells’ insulin secretion, and likewise prevent or delay disease progression and improve clinical outcome for patients.

The central role of Tregs in the control of the immune response has led to intensive research of Treg-based therapy to treat various immune dysfunctions.

We and others have shown recently that IL-2 can directly and specifically activate/expand Tregs. IL-2 is a soluble signalling molecule that regulates the activities of white blood cells (leukocytes, often lymphocytes). IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes, notably at the highest levels on Tregs. IL-2 given at low dose stimulates Tregs without stimulating other lymphocytes and thus could be an ultimate Treg stimulator for fighting autoimmune diseases.