The marathon runners of the immune system
When it comes to chronic infections and cancer, a particular type of immune cell plays a central role in our defenses. Researchers at the ÐÇ¿Õ´«Ã½ have uncovered the key to the tenacity of these immune cells in coping with the marathon that is fighting a chronic infection. Their results lay the foundations for more effective therapies and vaccination strategies.
06 March 2023 | Angelika Jacobs
Infected and abnormal cells have to go. And as quickly as possible, before any more damage is done. This is the task of what are known as cytotoxic T cells. The question of how these cells fight off chronic infection is under investigation by the team surrounding Professor Daniel Pinschewer at the Department of Biomedicine of the ÐÇ¿Õ´«Ã½ in collaboration with several national and international partners.
“These T cells can become specialized in two different ways: either as a kind of sprinter or as marathon runners,” explains Pinschewer. “However, the latter can also convert into sprinters at any time, in order to stamp out 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 into developing into sprinters, which can only intervene effectively in the short term to remove infected cells,” says the virologist. “If all T cells behaved like that, our immune defenses would break down pretty soon.”
Biological messenger counteracts the “shock”
In a study that is now published in the journal Immunity, the researchers examined how, in spite of this, the immune system is still able to provide enough 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 takes away the shock of the inflammation, so to speak,” explains Dr. Anna-Friederike Marx, lead author of the study.
In addition, the biological messenger causes the marathon T cells to proliferate, so that more endurance runners are available to combat the infection. “Thanks to IL-33, there are enough cytotoxic T cells around for the long haul that can still pull off 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 one key to improving cancer immunotherapy, to enable T cells to wage an efficient and long-lasting offensive against tumor cells.
Original publication
Anna-Friederike Marx, Sandra M. Kallert, Tobias M. Brunner et al.
Immunity (2023), doi: 10.1016/j.immuni.2023.01.029
