Immunity system complexity: aging T cells don't fade away (Introduction)

by David Turell , Thursday, September 22, 2022, 01:12 (576 days ago) @ David Turell

They remain tough:

https://medicalxpress.com/news/2022-09-killer-cells-age.html

"The human immune system is a thing of wonder. Up until now it had been widely assumed that the ability of killer T cells to destroy tumor cells and pathogens would deteriorate with age. It turns out, however, that the opposite is true—they become better killers, the older they get.

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"The older someone is, the more likely they are to get cancer. According to Germany's Robert Koch Institute, more than half of the approximately 500,000 people diagnosed with cancer every year are over the age of 60. As the coronavirus pandemic has shown all too clearly, viral infections tend to be more severe in older patients.

"This was thought to suggest that the human immune system becomes weaker with age and that the same must therefore be true of the killer T cells that play such a critical role in fighting off pathogens. The job of the T cell is to track down and kill virus-infected cells or tumor cells in the body. Up until now the accepted scientific view has been that T cells function less effectively as they age.

"However, researchers at Saarland University have now discovered that T cells turn into the ultimate killers as they get older. "We found the rather surprising result that the ability of cytotoxic CD8+ T cells to destroy tumor cells did not deteriorate but actually improved with age. When you compare the same number of young and old T cells, it is the older ones that are the better and more effective killers," said Dr. Annette Lis, a qualified pharmacist who has been working for many years in the group led by Professor Markus Hoth at the university's medical campus in Homburg.

"The reason that T cells are such effective killers has to do with the highly effective weapons that they have at their disposal. "The production of the molecules perforin and granzyme is enhanced in older T cells. As its name suggests, the molecule perforin perforates the target cells making tiny pores in the cell membrane. Granzyme can then enter the cells and initiate apoptosis—a form of programmed cell death," explained doctoral research student Dorina Zöphel.

"In addition, older experienced T cells have an accurate picture of who they are supposed to be targeting. Cytotoxic CD8+ T cells have a good memory of who they have attacked and destroyed in the past. And as part of our adaptive immune system, they live and learn. "The T cells are able to form memory cells. If they come into contact with a pathogen that they are already acquainted with, they respond very quickly and very effectively," said Dorina Zöphel.

"For a long time, older memory CD8+ T cells were not thought to be particularly suitable for immunotherapy and they therefore found only limited use. In younger cancer patients, these T cells are extracted from the patient's blood, trained in a Petri dish to fight the tumor cells and then reintroduced into the patient's body to fight the cancer."

Comment: this research points out powerful fighting molecules in T cells armory. They cannot be found by chance mutations. Only design fits.