Disable the "harmful" part of immunity
Scientists have achieved selective suppression of the immune system for the treatment of autoimmune diseases
LifeSciencesToday based on NIH materials: Research breakthrough selectively represses the immune systemAmerican scientists have developed a revolutionary technology for selectively inhibiting the part of the immune system responsible for attacking myelin, an insulating substance that envelops nerve fibers and makes possible electrical interaction between brain cells.
The system was tested on a mouse model of multiple sclerosis.
The cause of autoimmune diseases is the erroneous perception by T cells - one of the types of cells of the immune system – of the body's own tissues as foreign substances and an attack on them. Today, the treatment of autoimmune diseases involves the use of immunosuppressive drugs that suppress the activity of the entire immune system. These drugs increase the predisposition to infections and the risk of developing cancer, as the ability of the immune system to detect and destroy aberrant cells decreases.
Microglial cells (round) absorb oligodendrocytes (branched). This process is believed to occur in multiple sclerosis. Oligodendrocytes form insulating myelin sheaths around axons in the central nervous system. Microglia normally absorb cellular debris and bacteria as part of the body's immune response. In multiple sclerosis, it attacks oligodendrocytes, which may be provoked by a virus, in people with a hereditary predisposition. The destruction of the myelin sheath leads to the loss of nerve function. (SEM) (Photo: sciencephoto.com )
With the support of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) at the National Institutes of Health (NIH), Dr. Stephen Miller (Stephen Miller) and Lonnie Shea (Lonnie Shea) from Northwestern University (Northwestern University) together with researchers from the University of Sydney (University of Sydney) and the Myelin Repair Foundation have developed a new method of suppressing only that part of the immune system that is responsible for the development of autoimmune diseases.
The method is based on the natural principle of protection used by the body to prevent the activation of autoreactive T cells attacking healthy tissues. The results of the study are published in the online edition of the journal Nature Biotechnology (Getts et al., Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis).
"We are trying to do something that interacts with naturally occurring processes in the body," says Dr. Shi. "The body has natural mechanisms for suppressing an inadequate immune response, and in fact we are just looking for how to use them."
One of these mechanisms involves a constantly ongoing process of cleansing the body of apoptotic, or dying, cells. When a cell dies, it releases chemicals that attract certain cells of the immune system – macrophages. Macrophages absorb the dying cell and deliver it to the spleen, where autoantigens – the smallest fragments of proteins of the dying cell – are presented to the pool of T cells. To prevent the activation of autoreactive T cells, macrophages initiate the suppression of any T cells capable of binding to the presented autoantigens.
Dr. Miller and his colleagues were the first to demonstrate that this natural suppression mechanism of normally attacking myelin T cells can be used by binding a specific autoantigen, such as myelin, to apoptotic cells. His laboratory has spent decades demonstrating that they can achieve antigen-specific suppression of immunity in various animal models of autoimmune diseases. Recently, scientists, together with their colleagues in Germany, have started preliminary clinical trials to verify the safety of administration of antigen-associated apoptotic cells to patients with multiple sclerosis. Having confirmed the safety of their administration, the tests also revealed a key problem – the use of cells as a means of delivering antigens.
"Cell therapy is extremely expensive, as it must be carried out in a large medical center, where it is possible to isolate white blood cells in sterile conditions and inject antigen-bound cells back into the body of patients," explains Dr. Miller. "This is an expensive, complex and time-consuming procedure."
The solution to this problem – the development of a surrogate for apoptotic cells – was born in the collaboration of Miller's laboratory with a bioengineer from Northwestern University, Dr. Shi. The scientists linked the desired antigens to microscopic biodegradable particles (about 500 nm in diameter), which, as predicted, were absorbed by circulating macrophages similarly to apoptotic cells.
Surprisingly, when tested in Dr. Miller's laboratory, these antigen-bound particles induced T-cell tolerance in animal models of autoimmune diseases as well, if not better, as antigen-bound apoptotic cells.
Using their myelin-bound particles, the scientists were able to prevent both the onset of multiple sclerosis in animals with its model, and the progression of the disease if the particles were injected when the first clinical symptoms appeared.
In the near future, scientists hope to begin phase I clinical trials of their new technology. The material from which the particles are made has already been approved by the U.S. Food and Drug Administration and is currently being used in absorbable suture material, as well as undergoing clinical trials as a means of delivering anti-cancer drugs. Dr. Miller believes that proven safety along with the simplicity of particle production will bring their discovery closer to clinical practice.
"I think we have found a very powerful way to induce tolerance, which can be easily implemented in clinical practice. Now we are doing everything to speed up this process," says Miller.
As laboratory experiments have shown, in addition to the possibility of being used for the treatment of multiple sclerosis, this method can also be used for other autoimmune diseases, such as type I diabetes and specific food allergies. In addition, scientists believe, it may be useful to patients after transplantation who need to suppress the body's natural immune response to the transplanted organ.
Portal "Eternal youth" http://vechnayamolodost.ru20.11.2012