ETH ZURICH Original Study
Posted by Peter Rüegg-ETH Zurich on
When your body is in under oxidative stress, your immune system gets weaker. Exposure to UV radiation, air pollution, smoking, and drinking alcohol are all known to cause oxidative stress and the release of free radicals.
For the first time, researchers have shown that higher doses of vitamin E can mitigate the stress on immune cells.
Whenever a virus or other pathogen enters our bodies, a certain class of immune cells—the T cells—jump into action, proliferating rapidly.
One sub-class of these cells, the CD8+ T cells, eliminate the virus by killing cells it has infected. Other T cells, known as CD4+ T cells, coordinate the immune response to all kinds of pathogens. These are the generals in the immune system’s army.
But a week can pass before these T cells start to take their toll on a virus, because in the early stages of an infection too few T cells are able to recognize the specific pathogen.
Only once they have had “enemy contact” do these few “scout” cells begin to divide, forming “clones” of themselves. With cells dividing every eight to twelve hours, it takes a few days to gather a strike force of cells in the hundreds of thousands: enough to overwhelm the infection.
However, this immune response does not work if significant oxidative stress is damaging the T cells and depriving the body of the tools it needs to repair them, according to the new study published in the Journal of Experimental Medicine.
If the immune cells lack repair enzyme Gpx4 (or it is defective), the T cells die off as they divide, which means the immune system cannot eliminate the pathogen and the infection becomes chronic. This is the enzyme responsible for repairing oxidative damage to the cell membrane.
For the first time, researchers have shown that higher doses of vitamin E can mitigate the stress on immune cells.
One sub-class of these cells, the CD8+ T cells, eliminate the virus by killing cells it has infected. Other T cells, known as CD4+ T cells, coordinate the immune response to all kinds of pathogens. These are the generals in the immune system’s army.
But a week can pass before these T cells start to take their toll on a virus, because in the early stages of an infection too few T cells are able to recognize the specific pathogen.
Only once they have had “enemy contact” do these few “scout” cells begin to divide, forming “clones” of themselves. With cells dividing every eight to twelve hours, it takes a few days to gather a strike force of cells in the hundreds of thousands: enough to overwhelm the infection.
However, this immune response does not work if significant oxidative stress is damaging the T cells and depriving the body of the tools it needs to repair them, according to the new study published in the Journal of Experimental Medicine.
If the immune cells lack repair enzyme Gpx4 (or it is defective), the T cells die off as they divide, which means the immune system cannot eliminate the pathogen and the infection becomes chronic. This is the enzyme responsible for repairing oxidative damage to the cell membrane.
VITAMIN E TO THE RESCUE
When testing mice whose immune cells lacked the repair enzyme, researchers led by Manfred Kopf, a professor at ETH Zurich’s Institute of Molecular Health Sciences, were able to save the immune cells from cell death by mixing a high dose of vitamin E into the animals’ food.
That was enough antioxidant to protect the T cells’ cell membranes from damage, so they could multiply and successfully fend off the viral infection. At 500 milligrams per kilogram of mouse feed, this quantity of vitamin E was ten times higher than was present in the standardized normal food.
The researchers demonstrated this by way of a mouse model using animals in which the Gpx4 gene can be deactivated either cell-specifically or at a chosen point in time. These mice were developed by researchers at the Helmholtz Zentrum München. The ETH scientists then altered the mouse line so that the Gpx4 gene was inactive only in T cells or certain phagocytes.
That was enough antioxidant to protect the T cells’ cell membranes from damage, so they could multiply and successfully fend off the viral infection. At 500 milligrams per kilogram of mouse feed, this quantity of vitamin E was ten times higher than was present in the standardized normal food.
The researchers demonstrated this by way of a mouse model using animals in which the Gpx4 gene can be deactivated either cell-specifically or at a chosen point in time. These mice were developed by researchers at the Helmholtz Zentrum München. The ETH scientists then altered the mouse line so that the Gpx4 gene was inactive only in T cells or certain phagocytes.
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