Autoimmune diseases: we discovered how to turn white blood cells from attacking the body to protecting it
We have shown how to prevent immune cells from attacking the cells of the nervous system. LightField Studios / Shutterstock
For most of us, the immune system protects us from bacteria, viruses and other harmful pathogens. In people with autoimmune diseases, the body's white blood cells instead perceive and attack other cells and tissues in the body as a threat. While some immune disorders like allergies can sometimes be treated, autoimmune disorders like multiple sclerosis (MS) remain incurable.
Our research has shown that you can prevent the immune system from attacking the nerves - which is the case with MS. We did this by giving the immune system more and more doses of the same molecule that attacked the immune system.
Now we've gone a step further to show how this process works in the immune system's white blood cells. Our team revealed the complex mechanisms that allow us to switch T cells (a type of white blood cell) from attacking the cells of patients with autoimmune diseases to protecting them. We learned how to make reactive T cells tolerant.
Our T cells have evolved so that everyone recognizes different parts of the molecules made by pathogens (also known as antigens). When the T cells recognize antigens, the T cells begin to multiply to attack the intruders. The T cells change from a dormant state to a highly activated state by switching on immune response genes that help them attack pathogens.
When infection is over, some of these T cells remain, resulting in lifelong immunity as memory T cells. You can carry this lifelong memory by printing triggers on our chromosomes that can reactivate immune response genes much faster.
The immune system makes a mistake in autoimmune diseases such as MS, Graves' disease and type 1 diabetes. In MS, the T cells see the myelin basic protein, a component of the outer, insulating coating that surrounds the nerve cells, as an antigen. They attack the nervous system and as a result, MS patients lose control of their muscles. Our research tries to correct this.
Weaken T cells
To better understand this process, we focused on the T cells that specifically recognize the myelin base protein as an antigen. We found that these T cells became less reactive over time after exposure to gradually increasing doses of the basic myelin protein.
This progressive exposure reprogrammed these T cells so that the signals that prompted the cells to attack the protein became weaker. This converted the T cells from attack to protection.
White blood cells usually protect against diseases. microstock3D
This change could be explained by the fact that the immune system is regulated by two types of genes. One type directs the immune system to attack, while the other gene type silences the immune system to prevent it from getting out of control.
We have shown that when T cells are made tolerant, two of the most important genes that suppress the immune system have been reprogrammed at the chromosome level to keep them more active. Repeated exposure to the myelin base protein shaped a memory within these inhibitory genes. This allowed T cells to remember to prevent the T cell receptor from sending attack signals when they encountered the same specific myelin basic protein fragment.
The end effect of turning on the inhibitory genes was to weaken the signals in T cells that would normally turn on other genes that activate the immune system. This meant that the T cells no longer received the signal to attack nerve cells.
Autoimmune diseases are currently being treated with immunosuppressants. The problem with this is that they suppress the entire immune system and make the patient susceptible to cancer and other infections. Studies with antigen therapy in patients with MS and Graves' disease have not yet been completed. However, the results of short-term preliminary clinical studies showed that both MS and Graves' disease showed improvement in their health over the duration of the studies.
One day we hope that antigen-based immunotherapy can bring great benefits to all types of autoimmune diseases. By detailing the complex mechanisms that control the fate of self-reactive T cells, we may also have opened the door to more specific therapies for these diseases.
This article is republished by The Conversation under a Creative Commons license. Read the original article.
Peter Cockerill receives funding from the Medical Research Council to study the epigenetic reprogramming of genes in memory T cells. I have no conflict of interest regarding this article.
David Wraith advises Apitope International NV, a company focused on antigen-specific immunotherapy for autoimmune diseases, and receives funding from the Medical Research Council and the EU.
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