After an infection, T cells in our body multiply like mad
Researchers from the Netherlands Cancer Institute and the Leiden University Medical Center (LUMC) have created a tracking system that shows how often cells have divided. With this they discovered a hitherto unknown population of immune cells, namely young memory cells that behave like stem cells. It is precisely these cells that appear to play a crucial role in the rapid response of our immune system after a second infection with the same pathogen. Therefore, they are very interesting in view of the development of vaccines.
After an infection, T cells in our body multiply like mad. Much of this scours the body and kills cells that are infected. When the pathogen is cleared, most T cells die, but a small group of memory T cells remain. They provide long-term immunity.
The researchers, led by Ton Schumacher of the Antoni van Leeuwenhoek and Ferenc Scheeren of the LUMC, wanted to get to know this group of memory cells better. In particular, they wanted to settle a fundamental discussion about the question: does the group of memory cells consist of cells that have already divided many times and then undergone a rejuvenation course? Or are they cells that have always remained young, and have shared little, and therefore were able to survive.
Track errors
To find out, researchers Kaspar Bresser and Lianne Kok developed a tool to measure how often T cells have divided. They knew: with every cell division, mutations, or errors in the DNA, can occur. They could use those errors as tell-tale signs to measure the number of divisions. They therefore introduced an artificial piece of DNA into the T cell that is very sensitive to errors. As soon as an error occurs in this piece of DNA, the cell, and all its descendants, will turn red. “The greater the proportion of red cells in a population, the more that group of cells has divided,” Bresser said.
Baptized DivisionRecorder, this ‘error detector’ is the first of its kind. It can track hundreds of cell divisions, instead of the 5 to 8 divisions that conventional methods can measure.
Two groups of memory cells
The researchers injected the T cells with the error indicator into the blood of mice and followed closely what happened for two months. To their surprise, they saw that the memory cells were not one homogeneous group. Bresser: “We saw a group of memory cells with a large percentage of red cells, which had therefore already divided very often. These cells were very similar to the T cells that kill infected cells, and have probably done so before. We also discovered a group of young T cells that have kept themselves quiescent during the initial infection and behave like stem cells.” With this they brought a solution to the old discussion about the nature of memory cells: it is not either-or, but both are correct.
Young, fit, memory cells crucial in fighting reinfection
The researchers also saw that after a second infection with the same pathogen, especially these young memory T cells divide like crazy and fight the infection. Bresser: “This is the first evidence that memory T cells that have only shared little are crucial in reinfection.”
‘The cells you want after vaccination’
According to the researchers, this study underlines the importance of the young memory T cells that they have identified as the cells that you want to induce through vaccination. “The young memory T cells are very fit and powerful during reinfection. By better understanding how these cells look and work, we may be able to improve vaccinations and, for example, better determine when a booster vaccination can be given,” says Ferenc Scheeren.
Read more about the research in Nature Immunology
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