Understanding how T cells fight chronic infections

Understanding how T cells fight chronic infections
© shutterstock/Meletios Verras

Researchers from the University of Basel have discovered how immune cells can fight chronic infections over long periods of time.

When the body is subjected to chronic infections and cancer, cytotoxic T immune cells are vital in defining the immune system. Infected and abnormal cells need to be removed as quickly as possible to limit damage to the body; this is performed by T cells.

The University of Basel researchers wanted to understand how these cells can fight chronic infections. Professor Daniel Pinschewer at the Department of Biomedicine of the University of Basel led an international team of researchers to study cytotoxic T cells. The results of the study may help to accelerate the development of therapy and vaccination strategies.

T cells work together to kill chronic infections

The study ‘The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8+ T cells in chronic viral infection’ has been published in Immunology.

“These T cells can become specialised in two different ways: either as a kind of sprinter or as marathon runners. However, the latter can also convert into sprinters at any time in order to stamp out an infection,” said Professor Pinschewer.

When a patient has a chronic infection, T cells are activated, and a strong inflammatory response occurs simultaneously. This reaction shocks the T cells into a state of rapid activity, meaning they can only effectively remove infected cells in the short term. “If all T cells behaved like that, our immune defences would break down pretty soon,” explained Professor Pinschewer.

The role of IL-33

The researchers examined how the immune system can provide enough T cells against chronic infections over a long period of time, despite this rapid response. They found that the interleukin-33 (IL-33) protein is an essential part of the process. IL-33 acts as a biological marker that allows T cells to remain active for long periods.

“IL-33 takes away the shock of the inflammation, so to speak,” said Dr Anna-Friederike Marx, lead author of the study.

As well as this, IL-33 causes T cells to proliferate, meaning that more long-lasting cells are produced to fight 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,” said Marx.

The researchers believe their findings can improve the treatment of chronic infections such as hepatitis C. It is possible for IL-33 to be administered to chronic infection patients to support an effective immune response. The researchers have also hypothesised that IL-33 could be used to improve cancer immunotherapy. They believe the protein could enable T cells to provide efficient and long-lasting attacks against tumour cells.

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