Building a T Cell Army

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Study identifies antioxidant as being key to maintaining survival of disease-fighting T cells.
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T cells play a critical role in fighting viral infections, such as the flu, by eradicating cells that are infected with the virus.
Our immune systems generate an army of warrior cells that seek out and kill harmful bacteria and viruses. Known as ‘activated T cells’, these sentinels also produce potent chemicals that, in high levels, are used to kill cells and invaders, and in low concentrations, serve to promote growth of other T cells and maintain immune defenses.

These chemicals, known as reactive oxygen species (ROS), cause activated T cells to increase production of an antioxidant known as glutathione (GSH). Until recently, researchers were not clear how this affected the immune response.

Dr. Dirk Brenner from the Luxembourg Institute of Health in collaboration with PM Senior Scientist Dr. Tak Mak have revealed the effect that GSH has on T cells by developing an innovative experimental model. The model enabled researchers to turn off GSH production in activated T cells.
 
The results showed that T cells lacking GSH, while still able to become activated and attack intruders, where unable to generate the energy needed to survive in the long term. “We found that when GSH production was blocked in activated T cells, levels of key proteins required to break down nutrients for energy were lowered, and that the cells eventually died,” said Dr. Mak.
 
Furthermore, the team explored the effect GSH on the ability of the immune system to fight invaders: when GSH production was blocked, the immune system was less able to effectively clear viral infections. 
 
These findings may also be important to autoimmune diseases. Shutting off GSH production in an experimental model of multiple sclerosis—where T cells are abnormally overactive—prevented the development of the disease. 
 
This study highlights an unexpected role for GSH in maintaining a robust army of activated T cells that can effectively fight disease.
 
Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, Binsfeld C, Hao Z, Brüstle A, Itsumi M, Jäger C, Chen Y, Pinkenburg O, Camara B, Ollert M, Bindslev-Jensen C, Vasiliou V, Gorrini C, Lang PA, Lohoff M, Harris IS, Hiller K, Brenner D. Glutathione primes T cell metabolism for inflammation. Immunity. April 2017.doi: 10.1016/j.immuni.2017.03.019.
 
This work was supported by the National Research Fund Luxembourg, the National Institutes of Health, the German Research Council, the Deutsches Zentrum für Infektionsforschung, the University Hospital Giessen Marburg, the National Multiple Sclerosis Society, the Canadian Institutes of Health Research and The Princess Margaret Cancer Foundation. T Mak holds a Tier I Canada Research Chair in Inflammation Responses and Traumatic Injury.