T cells are the killers of the immune system, but like all good soldiers, they need experience before they can perform effectively. Indeed, T cells that have fought a particular infection before are much better than their inexperienced counterparts at clearing it from the body. This much scientists have long known. But new research suggests that there is more to the story. Researchers have discovered that some seemingly naive T cells are just as effective against infection as their experienced brethren.
Immunologist Sara Hamilton of the University of Minnesota and her colleagues challenged the immune systems of mice by exposing them to radiation. They then introduced fresh T cells that had been cultured in the lab into their immune system. These T cells somehow recognized that they were few in number and began to proliferate.
The scientists then exposed these new T cells, along with regular na¿ve T cells and experienced T cells to the pathogen: Listeria monocytogenes, which can produce flulike symptoms in humans. The proliferated T cells killed the Listeria just as well as their peers with prior memory of the microbe.
"The memory cells have this heightened ability to protect us, they have a better capability of dealing with recurrent infection," Hamilton explains. "These [proliferated] cells are able to do that [even] though they've never been primed to see the antigen. On a per cell basis, they were just as good as the real memory cells."
These false-memory T cells raise further questions: to be effective infection fighters, the cells needed to proliferate in the presence of their immune cell counterparts or be genetically modified to fail to produce the TRAIL molecule, a protein linked to programmed cell death. "The part we don't know is how that TRAIL molecule is working," Hamilton says. It may be that other secreted proteins, such as cytokines, are equally important as well.
The finding could, however, provide a new pathway for boosting otherwise damaged immune systems. If radiated mice can create false memories in transplanted T cells that improve their infection-fighting performance, it may be that radiated cancer patients or others whose immune systems are compromised can do the same. The research appeared in yesterday's Nature Immunology.