BCG vaccine against type 1 diabetes

In experiments on blood cells of patients with type 1 diabetes and other autoimmune diseases, scientists at the Massachusetts General Hospital, working under the guidance of Dr. Denise Faustman, demonstrated that blocking one of the mechanisms regulating the immune system leads to the selective destruction of immune cells attacking the body's own tissues.

Previously, the authors demonstrated the possibility of curing type 1 diabetes in a mouse model. The results of the latest work confirmed the effectiveness of this approach to human cells and formed the basis of the phase I clinical trials currently underway.

Type I diabetes and other immune diseases develop when immune cells mistakenly attack the body's own cells. Over the past 10 years, within the framework of several studies, the authors have shown that triggering the expression of the immune system modulator tumor necrosis factor (TNF) in mice with type 1 diabetes leads to the death of T-lymphocytes that destroy insulin-producing pancreatic islets. After such treatment, the animals regenerated healthy islet cells capable of synthesizing a normal amount of insulin, which ensured a complete cure of diabetes.

In the latest work, the researchers used T-lymphocytes from more than 1,000 patients with type 1 diabetes and other autoimmune diseases, as well as healthy individuals as controls. First, they found that treatment with tumor necrosis factor destroys CD8 T-lymphocytes (so-called T-killers) of diabetic patients, but does not affect CD4 T–helper T-lymphocytes. Tumor necrosis factor also induced the death of CD8 T cells in patients with other autoimmune diseases, but did not have a negative effect on the cells of healthy people.

Since tumor necrosis factor interacts with the immune system using two types of receptors, TNFR1 and TNFR2, activating two different signaling mechanisms, the scientists decided to test a number of tumor necrosis factor agonists – compounds with TNF-like activity. One of the tested agonists interacts with TNFR1 expressed on all T lymphocytes, and the other three interact with TNFR2 expressed only on certain subpopulations of T cells. Only one of the agonists interacting with TNFR2 triggered the selective death of a certain subtype of T-killers in patients with diabetes and other autoimmune diseases. At the same time, in samples with cells of healthy individuals, as well as under the influence of tumor necrosis factor, cell death was not observed at all.

Further experiments on blood samples of several patients with type 1 diabetes showed that the CD8 cell population responsible for the destruction of insulin-producing pancreatic cells in all cases dies under the action of TNFR2 agonist, while a similar population of cells of healthy people under these conditions proliferates. However, CD8 T lymphocytes of diabetic patients directed against two common viruses did not die under the action of TNFR2 agonist, which confirms the selective death of cells responsible for the autoimmune reaction.

As part of the ongoing phase I clinical trials of the approach proposed by the authors to the treatment of type 1 diabetes, experts are checking whether the use of Calmette-Guerin bacilli (BCG), the introduction of which temporarily increases the level of tumor necrosis factor, can reduce the number of autoimmune T cells in patients with type 1 diabetes. They are also working to find out the optimal dosages and administration schemes of the drug.

Portal "Eternal youth" www.vechnayamolodost.ru based on ScienceDaily – Potential Diabetes Treatment Selectively Kills Autoimmune Cells From Human Patients 

01.10.2008