Secret of our body’s inner assassins uncovered by University of Cambridge researchers

They are the trained assassins within our body - able to kill and kill again.

Now University of Cambridge scientists have discovered the secret of how T cells are able to repeatedly reload their toxic weapons.

In the longer-term, it is hoped the discovery could help us design and engineer T cells that are more effective at killing cancer cells.

A teaspoon of our blood is believed to have about five million T cells, measuring just 10 micrometres in length or about a tenth the width of a human hair.

But they pack a punch.

Cytoxic T cells are specialist white blood cells that our immune system trains to recognise and take out threats, including invading viruses and tumour cells.

This ability is harnessed by existing immunotherapies that are being used in the fight against cancers.

Prof Gillian Griffiths, from the Cambridge Institute for Medical Research, who led the research, said: “T cells are trained assassins that are sent on their deadly missions by the immune system.There are billions of them in our blood, each engaged in a ferocious and unrelenting battle to keep us healthy.

“Once a T cell has found its target, it binds to it and releases its toxic cargo. But what is particularly remarkable is that they are then able to go on to kill and kill again. Only now, thanks to state-of-the-art technologies, have we been able to find out how they reload their weapons.”

In their research, published in Science and funded by Wellcome, the team showed that mitochondria are responsible for regulating the refuelling of T cells’ toxic weaponry.

While they are better known for acting like the battery powering the functions of our cells, here they are using an entirely different mechanism

Prof Griffiths explained: “These assassins need to replenish their toxic payload so that they can keep on killing without damaging the T cells themselves.

“This careful balancing act turns out to be regulated by the mitochondria in T cells, which set the pace of killing according to how quickly they themselves can manufacture proteins.

“This enables killer T cells to stay healthy and keep on killing under challenging conditions when a prolonged response is required.”

Footage showing killer T cells as they hunt down and eliminate cancer cells has been released by the researchers.

In it, the cells are seen as red and green amorphous blobs that move around rapidly, investigating their environment.

But when one finds an infected cell or, as in the footage, a cancer cell, membrane protrusions rapidly explore the surface of the cell, looking for signs that this is an invader.

The T cell binds to the cancer cell, injecting poisonous cytotoxic proteins down special pathways called microtubules to the interface between the T cell and the cancer cell, before it punctures the surface of the cancer cell in order to deliver the deadly cargo.

Read more

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