Study in PNAS found that natural killer cells, once activated, have a better response when activated a second time.

The body’s innate immune system contains cells that can learn from experience and attack pathogens more effectively a second time around, according to researchers at Washington University School of Medicine in St. Louis. Scientists previously thought any such ability was limited to the immune system’s other major branch, the adaptive immune system.

“We’re calling this new property ‘memory-like’,” says senior author Wayne M. Yokoyama, M.D., the Sam J. and Audrey Loew Levin professor of medicine. “Natural killer cells can’t specialize in recognition of a particular pathogen, but we found that once they’ve been activated, they can respond more easily and effectively to the next call for activation.”

Previous efforts to learn what happens to natural killer cells in the innate immune system after activation have been hampered by the fact that the cells do not return to a resting state in cell cultures, which shortens their already brief life spans. To circumvent this problem scientists activated mouse natural killer cells in culture, stained them with a fluorescent green dye, and injected them back into the mice.

The team tracked the cells and re-extracted them one to three weeks later. They found the cells had returned to their resting state but could be reactivated more easily and responded more vigorously to activation. Improved responses included increased cell replication and production of interferon gamma, a compound that has antipathogen activities and helps spread the immune response by activating additional immune cells. This appeared to be true of both the original cells and their descendants, identifiable by reduced levels of green dye.

The team notes that in newborns and young infants the adaptive immune system is largely unavailable. They speculate that it may one day be possible to help the body defend itself during this period by finding a way to prime this memory-like mechanism in natural killer cells.

“Other innate immune cells may also have similar properties,” Dr. Yokoyama says. “It should be possible to therapeutically exploit these memory-like properties to make more effective immune cells.”

The findings are published online this week in the Proceedings of the National Academy of Sciences.


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