“This is probably one of the most amazing papers in immunology I’ve seen in the last decade,” says John Werry, director of the Immunology Laboratory at the University of Pennsylvania Perelman School of Medicine. study. “It tells us that immunity can Unbelievably It is durable once you understand how to generate it properly. ”
Andrew Sorens The postdoc immunologist who took over immunizations for Project 21 didn’t expect it to become his main responsibility. “I felt like it could have been the worst project ever because the endpoint wasn’t thought out. Or it could have been pretty cool because it was interesting biology,” he recalls. .
This project is not like a researcher writing a grant application. This is a study that threatens to overturn the stereotype that T cells are inherently limited in their fighting capacity, and there is no guarantee of success. “It’s almost a monumental experiment in history. No one does an experiment that lasts 10 years,” he says Wherry. “This is in contrast to funding mechanisms and five-year funding cycles, which means you have to do something new every three years. This is in contrast to the way we train students and postdocs who are in high demand, which is in contrast to the short attention spans of scientists and the scientific environments we live in. Therefore, we want to address very important problems. It really shows what it means.”
In fact, the project was unfunded for the first eight years and ran solely on the spare time of lab members. But its central question was ambitious: Should immune cells age? ) can only split a limited number of times. In the 1980s, researchers advanced the idea that this could occur through the erosion of protective telomeres (a type of aglet at the ends of chromosomes). This telomere shortens when the cell divides. After enough divisions, there are no more telomeres left to protect the genes.
The project pushed Hayflick’s boundaries and quickly took up most of Soerens’ time. He rushed to a colony of mice to immunize, collect samples, and start a new cohort of T-cell armies. He counted the cells, analyzed the mixture of proteins they produced, and recorded what changed over the years. It may indicate a mutation.
One day, the change was noticeable. A high-level protein associated with cell death called PD1. This is usually a sign of cell exhaustion. However, these cells were not exhausted. They continued to multiply, fight microbial infections, and form long-lived memory cells. All these features were viewed by the lab as markers of fitness and longevity. “It was a bit of a shock,” he says Soerens. “It was probably the first time I was convinced that this was true. something”
So the lab went on and on. Finally, Masopust said: Ten years, or four lifetimes, felt right. “The extreme nature demonstration was a good enough place for me.” (For the record: all of these cell cohorts are still in progress.)
