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The Jedi Cells: Fighting For Science

The Jedi Cells: Fighting For Science

by Mariska Willemsen

Superresolution image of killer T-cells surrounding a cancer cell. // image credit: NIH Image Gallery

Superresolution image of killer T-cells surrounding a cancer cell. // image credit: NIH Image Gallery

Turning your own immune system against you. A great new scientific tool. A research group at the Icahn School of Medicine in New York used some intrinsic properties of CD8+ T cells to be able to selectively destroy all sorts of cell types. The CD8+ T-cells, also known as ‘Killer T-cells’, patrol the body and kill infected cells. They are able to do this by selectively binding their T-cell receptors to so-called major histocompatibility (MHC) class one structures on the cell. T-cells can usually only recognize one specific type of MHC which makes them capable of killing only certain types of infected cells.
So how, and why, did they create these specified killer T- cells?
To first answer the how: The research groups used this ability of the killer cells to their advantage by creating T-cells which specifically bind to enhanced green fluorescent proteins (EGFP). EGFP is a tool often used in science to visualize whatever it is stuck to with a microscope. The created T-cells were named Jedi cells, or ‘just EGFP death-inducing’ cells. 
Now that these cells were created, how are they being used to help science?  Why were they created in the first place?
 

The beauty of these cells is that they can very specifically destroy cells which have  EGFP bind to them, What is even more convenient is that there are already many mice available with this EGFP inside them bound to specific cell types. Furthermore, the EGFP protein is fluorescent which means they are able to watch the destruction and have a visual control whether all cells are definitely gone. Therefore these T-cells can be used to study the function of different cell types by teminating them and see what happens to the animal. Furthermore it can be used to discover new ways in which T-cells interact with specific groups of cells which can teach us more about the immune system. Finally they can be used to imitate human diseases in mice.
They show in their article several examples of how they used these Jedi cells. For instance they used them to destroy insulin (important in glucose regulation) producing cells to investigate whether this would lead to the mice developing diabetes. This would in theory work since people with diabetes have a chronic insulin deficiency. They showed that indeed the cells were all destroyed, and the mice lost glucose control, which indicated diabetes.


This is just one of the possibilities, but as long as there are genetically encoded mice for your cell type, the possibilities are endless. This technique could prove very useful in discovering all types of interesting cell functions, pathways, and could be invaluable to mimic diseases in mice which can be used in pharmacological research.
An important question remains: why would they name cells killing everything Jedi cells instead of Sith cells?
Source: Agudo J, Ruzo A, Park ES, et al. GFP-specific CD8 T cells enable targeted cell depletion and visualization of T-cell interactions. Nature Biotechnology 2015;33(12):1287-1292.

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