Bystander T Cells May Play A More Active Role in Managing Type 1 Diabetes


There are many types of cells that all play a different role in how the body works. Some of these cell functions are very well known, while others are still somewhat mysterious. For years, scientists have thought that bystander T cells were just that – bystanders, since it was unclear what their exact purpose was. A team of researchers led by Matthias von Herrath, M.D., a professor in the La Jolla Institute for Allergy and Immunology’s Division of Developmental Immunology and a diabetes researcher, may have shed more light on what these cells actually do.

von Herrath and his team found that while the initial belief was that bystander T cells increased inflammation associated with type 1 diabetes and the destruction of insulin-producing islet cells, they may actually do quite the opposite. They found that these cells interfere with the destruction of pancreatic beta cells rather than supporting it. CD8+ cytotoxic T lymphocytes (CLTs) target specific protein fragments in islet cells and then destroy the cells. During this process, the pancreata are flooded with other T cells that do not detect protein fragments, which are referred to as the bystander T cells.

New studies by von Herrath and his team have discovered that in mouse models, the bystander T cells actually have an immunosuppressive effect and decrease the effect of cell-killing CLTs. When mice were injected with equal amounts of cell-killing and bystander CLTs, the researchers found that there was “little cell death, and the specific CLTs recruited to the pancreas became less harmful.” When decreased amounts of bystander cells were injected, there was more cell destruction as well as the occurrence of diabetes symptoms including hyperglycemia. Two possible theories are that bystander T cells limit access to beta cells as they flood the cell protecting them from cell-killing CLTs, or possibly that the bystanders interfered with the signals sent to cell-killing CLTs, so, therefore, the destruction is not as severe.

The study demonstrates that regulatory T cells are not the only cells that help counteract inflammation, though they are the most widely recognized for having this effect. With this new insight into bystander T cells, researchers may be able to leverage them in future treatment for type 1 diabetes. Additional research is necessary to explore this potential.

The Diabetes Research Connection, for which von Herrath is a member of the Scientific Review Committee, is committed to supporting novel research studies for type 1 diabetes. The DRC provides funding to support early career scientists in carrying out research projects geared toward preventing and curing type 1 diabetes as well as minimizing complications and improving quality of life for those living with the disease. Click to learn more about current projects and provide support.

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