Biology

Newly discovered “rogue hybrid” immune cell the potential trigger for type 1 diabetes

Newly discovered “rogue hybrid” immune cell the potential trigger for type 1 diabetes
Colorized scanning electron micrographs of a B and T immune cells shown with a fluorescent microscopy image of the previously unseen new "hybrid" cell, thought to play a major role in the onset of type 1 diabetes
Colorized scanning electron micrographs of a B and T immune cells shown with a fluorescent microscopy image of the previously unseen new "hybrid" cell, thought to play a major role in the onset of type 1 diabetes
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Computer simulation showing the extremely tight binding to an immune system cell of a peptide (blue) produced by the newly discovered “X lymphocyte.” The protein may direct the mistaken destruction of healthy insulin-producing cells in the pancreas, and in turn, cause type 1 diabetes. This autoimmune response is 10 times stronger than that seen with a weaker-binding, lab-engineered insulin mimic (red) that is itself 1,000 times more immune stimulating than normal insulin
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Computer simulation showing the extremely tight binding to an immune system cell of a peptide (blue) produced by the newly discovered “X lymphocyte.” The protein may direct the mistaken destruction of healthy insulin-producing cells in the pancreas, and in turn, cause type 1 diabetes. This autoimmune response is 10 times stronger than that seen with a weaker-binding, lab-engineered insulin mimic (red) that is itself 1,000 times more immune stimulating than normal insulin
Colorized scanning electron micrographs of a B and T immune cells shown with a fluorescent microscopy image of the previously unseen new "hybrid" cell, thought to play a major role in the onset of type 1 diabetes
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Colorized scanning electron micrographs of a B and T immune cells shown with a fluorescent microscopy image of the previously unseen new "hybrid" cell, thought to play a major role in the onset of type 1 diabetes

A new study, led by researchers from the Johns Hopkins University School of Medicine, has described the discovery of a new kind of immune cell that is hypothesized to play a fundamental role in the development of type 1 diabetes, and could be involved with other autoimmune disorders, such as multiple sclerosis.

Up to 10 percent of all diabetes cases are classified type 1. Primarily diagnosed in children, this chronic condition is considered to be an autoimmune disorder whereby the body's immune cells malfunction and destroy its insulin-producing beta cells. What mechanism actually drives this process is still unclear, but Abdel-Rahim A. Hamad from Johns Hopkins Medicine believes his new research may have finally cracked the mystery.

Our adaptive immune system primarily fights its battles using two types of white blood cells, or lymphocytes, called T and B cells. The research describes a newly discovered type of lymphocyte known as a dual expresser (DE). This unique DE cell possesses the ability to express both B cell receptors and T cell receptors.

"The cell we have identified is a hybrid between the two primary workhorses of the adaptive immune system, B lymphocytes and T lymphocytes," explains Hamad. "What is unique about the entity we found is that it can act as both a B cell and a T cell. This probably accentuates the autoimmune response because one lymphocyte is simultaneously performing the functions that normally require the concerted actions of two."

Recruiting a team of computational biologists from the IBM Research Center, a variety of computer simulations revealed how this DE immune cell could be triggering the onset of type 1 diabetes. A peptide, uniquely produced by DE lymphocytes, was found to amplify T cell attacks on insulin-producing beta cells, effectively explaining the connection with type 1 diabetes.

Computer simulation showing the extremely tight binding to an immune system cell of a peptide (blue) produced by the newly discovered “X lymphocyte.” The protein may direct the mistaken destruction of healthy insulin-producing cells in the pancreas, and in turn, cause type 1 diabetes. This autoimmune response is 10 times stronger than that seen with a weaker-binding, lab-engineered insulin mimic (red) that is itself 1,000 times more immune stimulating than normal insulin
Computer simulation showing the extremely tight binding to an immune system cell of a peptide (blue) produced by the newly discovered “X lymphocyte.” The protein may direct the mistaken destruction of healthy insulin-producing cells in the pancreas, and in turn, cause type 1 diabetes. This autoimmune response is 10 times stronger than that seen with a weaker-binding, lab-engineered insulin mimic (red) that is itself 1,000 times more immune stimulating than normal insulin

On top on this observation, further study revealed the presence of these unique hybrid immune cells, and its associated peptide, in the blood of patients with type 1 diabetes. Levels of these molecules were found in consistently higher numbers in type 1 diabetic patients than in the blood of non-diabetic subjects.

It is still very early days for the research with much more work to be done, both in understanding the link between this new immune cell and type 1 diabetes, and in comprehensively defining it. As well as paving the way for a possible diagnostic test that can identify patients at a high risk of developing type 1 diabetes, the research suggests new ways the illness could be treated. If the connection proposed by this study is validated, then the future could bring immunotherapy treatments that can specifically target these DE immune cells, and either eliminate them or stifle their ability to trigger the condition in the first place.

Hamad compares his team's discovery to finding something akin to a biological Loch Ness monster. Many experts in the field reportedly suggested this kind of rogue hybrid immune cell simply did not exist.

"We were willing to take the risk and look at something different, and now we may have taken the first steps toward finding new strategies to cure type 1 diabetes," says Hamad. "We also may one day find that DE cells are involved in the pathology of other autoimmune disorders such as multiple sclerosis and rheumatoid arthritis."

The new research was published in the journal Cell.

Source: Johns Hopkins Medicine

1 comment
1 comment
amazed W1
How marvellous to hear about a researcher who understands the difference between causal and coincidental effects that they have observed, and is proceeding with appropriate caution! Hamad deserves congratulations on this alone apart from the observation itself. Let's hope others in the medical academia don't start that amazing dialogue that so often happens when something original/new is discovered or proposed, i.e. that Hamad has not quoted any reference or learned paper or author on the the topic....