Training immune cells not to attack their fellow cells


T cells (red in this scanning electron microscope image) attack the body’s own cells in autoimmune diseases, but research has found that they can be retrained to stop these attacks. — NIAID

The body’s immune system can be re-wired to prevent it from recognising its own proteins, which, when attacked by the body, can cause autoimmune diseases like multiple sclerosis (MS), a significant new study by British scientists has found.

Autoimmune diseases are caused when the immune system loses its normal focus on fighting infections or disease, and instead begins to attack otherwise healthy cells within the body.

In the case of MS, the body attacks proteins in myelin – the fatty insulation-like tissue wrap-ped around nerves – which causes the nerves to lose control over muscles.

Led by a multi-disciplinary team from the University of Birmingham, scientists examined the intricate mechanisms of the T cells (a type of white blood cell) that control the body’s immune system and found that these cells could be “retrained” to stop them from attacking the body’s own cells.

For MS, this would prevent the body from attacking the Myelin Basic Protein (MBP) by reprogramming the immune system to recognise the protein as part of itself.

Supported by the UK Medical Research Council, the two-part study, published on June 9 (2020) in the journal Cell Reports, was a collaboration between two research groups led by Professor Dr David Wraith from the university’s Institute of Immunology and Immunotherapy, and Prof Dr Peter Cockerill from the university’s Institute of Cancer and Genomic Sciences, respectively.

The first stage, led by Prof Wraith, showed that the immune system can be tricked into recognising MBP by presenting the system with repeated doses of a highly soluble fragment of the protein that the white blood cells respond to.

By repeatedly injecting the same fragment of MBP, the process whereby the immune system learns to distinguish between the body’s own proteins and those that are foreign can be mimicked.

The process, which is a similar type of immunotherapy to that previously used to desensitise people against allergies, showed that the white blood cells that recognise MBP switched from attacking the proteins to actually protecting them.

The second stage saw gene regulation specialists led by Prof Cockerill probe deep within the white blood cells that react to MBP to show how genes are rewired in response to this form of immunotherapy to fundamentally reprogramme the immune system.

The repeated exposure to the same protein fragment triggered a response that turns on genes that silence the immune system, instead of activating it.

These cells then had a memory of this exposure to MBP embedded in the genes to stop them from setting off an immune response.

When T cells are made tolerant, other genes that function to activate the immune system remain silent.

Prof Wraith says: “These findings have important implications for the many patients suffering from autoimmune conditions that are currently difficult to treat.”

Prof Cockerill adds: “This study has led us to finally understand the underlying basis of immunotherapies that desensitise the immune system.”

Further longer term clinical trials will be needed to determine whether antigen-specific immunotherapies can indeed deliver lasting benefits to patients.

“If this is successful, this study will be the first defining the actual mechanisms of how T cells can be made tolerant to the body’s own proteins in a context that may lead to further advances in the battle to overcome autoimmunity,” Prof Cockerill says.

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