Adaptive immune cells like B and T cells aren't the only players in the immune system that can recognize antigens months after initially responding to them. A study published online in Nature today identifies a specific ligand-receptor interaction through which natural killer cells, part of the innate immune system and the body's first line of defense against immune invaders, remember and recognize antigens in the long-term.

The study, led by Lewis Lanier at the University of California, San Francisco, traced mouse natural killer (NK) cells that had a receptor for cytomegalovirus, monitoring cell populations during and after the mice were infected with the virus. The researchers discovered that, after the initial infection, where NK cells proliferated 1000-fold in the spleen and liver, the cells persisted in the immune organs for several months. Further, when those NK cells were injected into a new mouse, which was then infected with the virus, the cells conferred resistance.

"We haven't seen a limit yet" to how many times the cells can be transferred and still cause immunity, Lanier told The Scientist. In follow-up work his lab has been able to transfer the cells three times and the individuals still display resistance to the virus.

According to a long-held understanding of the immune system, NK cells, once activated, only survived for a few weeks at most until the adaptive immune system kicked in. A study from 2006 showed that NK cells launched an immune response to hapten (a protein that can trigger the immune system) in mice that couldn't produce T or B cells. However, that study did not suggest a mechanism for such an NK response.

NK cells only have receptors for about 20 specific antigens, and each individual's NK cells possess a unique set of 20 receptors. Without knowing a specific ligand and receptor, researchers had no way to specifically activate NK cells. With a specific ligand-receptor relationship (in this case the ligand and receptor for cytomegalovirus) on the NK cells the researchers in this study were able to trigger the NK cell response and then watch what the NK cells did over time.

If NK do indeed have a long term memory for antigens, researchers may be able use them to design vaccines. The advantage of an NK cell-based vaccine is that NK cells launch a quicker immune response than T or B cells. "And the frequency of NK cells is more than T cells," Lanier added.


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