Research co-funded by our BRC has identified a cell-killing mechanism in a specialised immune cell, which defies the conventional view of how the immune system works.

The study, published in Nature Immunology, looked at Gamma Delta T cells, discovering that they have a unique device which checks whether cells are dangerous or healthy. Crucially, they found that the cells can not only check the cells, but actually kill dangerous cells themselves.

Until now, it had been thought that these two jobs were done by different parts of the immune system. The ‘innate’ immune system has cells which identify broad problems across the body, while the adaptive immune cells track down and attack dangerous cells. But the mechanism identified by the study shows that Gamma Delta T cells are doing both of these jobs themselves.

“These maverick immune cells act as judge, jury and executioner, identifying and killing potentially dangerous cells in the body,” says Professor Adrian Hayday, whose teams at the Crick and King’s led the latest study. “This discovery was a huge surprise. It fundamentally changes our understanding of how the immune system makes critical judgement calls about when to act and when to hold back. This could open up exciting possibilities for treating disease.”

The new research found that the cells use two different checks to make sure they don’t kill a healthy cell. They checking if the cell looks dangerous but also whether it is functioning normally. This double-checking mechanism prevents the immune system from attacking healthy tissue. They also seem to adapt these checks depending on where in the body they are.

Understanding the way the Gamma Delta T cells work could lead to new treatments that mobilise the immune cells, for instance, to target and kill cancer cells. Adrian is working with GammaDelta Therapeutics, a spin-out company that was based on BRC-funded research, to apply the findings clinically.

The research was supported by Cancer Research UK, the UK Medical Research Council, Wellcome, the Guy’s and St Thomas’ Charity and the National Institute for Health Research Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London.

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