The marathon runners of the immune system

When it comes to chronic infections and cancer, a certain type of immune cell plays a central role in our defenses. Researchers from the University of Basel have discovered the key to the tenacity of these immune cells in dealing with the marathon fighting a chronic infection. Their results lay the foundation for more effective therapies and vaccination strategies.

Infected and abnormal cells should disappear. And as quickly as possible, before any more damage is done. This is the task of so-called cytotoxic T cells. The question of how these cells fight chronic infections is being investigated by the team around Professor Daniel Pinschewer from the Department of Biomedicine at the University of Basel, in collaboration with several national and international partners.

“These T cells can specialize in two different ways: as a kind of sprinter or as a marathon runner,” Pinschewer explains. “However, the latter can also transform into sprinters at any time in order to eradicate an infection.”

Chronic infections are a special case: the T cells are activated and a strong inflammatory response occurs at the same time. “This tends to ‘shock’ the T cells and develop them into sprinters, which can only intervene effectively in the short term to remove infected cells,” says the virologist. “If all T cells behaved this way, our immune defenses would break down quite quickly.”

Biological messenger counteracts the ‘shock’

This is evident from a study that is now published in the journal Immunity, the researchers investigated how the immune system can nevertheless supply sufficient T cells for the endurance race against chronic infections. According to their results, a biological messenger called interleukin-33 (IL-33) plays a key role. It allows the T cells to remain in their ‘marathon runner’ state. “IL-33 essentially takes away the shock of inflammation,” explains Dr. Anna-Friederike Marx, lead author of the study, explains.

In addition, the biological messenger causes the marathon T cells to multiply, making more endurance runners available to fight the infection. “Thanks to IL-33, there are enough long-term cytotoxic T cells that can still make a final sprint after their marathon,” says Marx.

The findings could help improve the treatment of chronic infections such as hepatitis C. It is conceivable that IL-33 could be administered to support an effective immune response. Thinking along the same lines, IL-33 could be a key to improving cancer immunotherapy, allowing T cells to mount an efficient and long-lasting offensive against tumor cells.

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