The microscopic "killer" cells that help us stay healthy have been captured on film with high resolution 4D imaging. Cytotoxic T cells (CTLs), found in our blood, target infectious cells such as cancer cells that might make us ill. Now researchers have got a closer look at how they work.
Cytotoxic T cells are a specialised type of white blood cell also known as "killer T cells". There are billions of them in our blood, with one teaspoon thought to contain five million T cells. "We really wanted to understand how these cytotoxic T cells are moving in for the kill, and what's going on inside these cells to make them work," said lead author of the study published in Immunity, professor Gillian Griffiths from the University of Cambridge.
"Until now, killer cells have only been filmed in 2D, so it has not been possible to discern events inside these cells clearly as all we had were flat images," added Griffiths, who explained that their high resolution 4D imaging offered a much closer look at these killer cells' sniper strategy.
In the video, the cytotoxic T cells show up as orange or green blobs, and the cancer cells are blue. A cytotoxic T cell is around 10 micrometres in length. Once it is sure of its target, it hones in and rapidly explores the surface with something that looks like a miniature snout. After this initial investigation, the T cell moves in for the kill. It latches onto a blue cancer cell, and injects a poisonous load of proteins known as cytotoxins (which show up as red on the video) into the cancer cell.
"These cytotoxic T cells use a really unusual secretion mechanism, which allows the killer cells to just target the cancer and the virally infected cells, without killing any of the innocent bystander cells that they have to squeeze through as they patrol the body," Griffiths said.
In order to capture the images, the researchers used high-resolution, 3D time-lapse multi-colour imaging, using microscopy techniques known as spinning disk confocal microscopy and lattice light sheet microscopy. "The confocal takes a single plane of the cell in high resolution, while the spinning disk allows you to capture many of those cells rapidly," said Griffiths, who explained that this allowed them to create a 3D image of the whole cell in 20 seconds.
Understanding the mechanisms of these cells has potential further applications. Ultimately, the researchers want to apply their understanding of how these killer cells work so that they that they can manipulate them for use in future cancer treatments. "By elucidating the changes inside these cells that lead to killing, we will be able to find out why killer cells cannot control some cancers, and identify ways in which killer cells can be made more effective," said Griffiths.