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A Killer Memory

17 April 2006 (All day)
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Ulrich von Andrian

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Natural killer cells are among the immune cells (white spheres) recruited to a blood vessel (black channel lined with red) in the ear when they encounter a previously seen antigen.

The immune system just got a memory upgrade. Immunologists have long thought that only the body's T and B cells were able to "remember" previously encountered pathogens, but new research indicates that another class of cells--called natural killer cells--can perform a similar feat. This newly recognized ability may play a role in everything from allergies to defending the body against cancer.

Vertebrate immune responses are thought to fall into two categories. Innate immunity is present from birth and is comprised of barriers such as the skin and mucous, as well as some immune cells such as natural killer (NK) cells. Its main goal is to broadly defend the body against a wide range of pathogens. Adaptive immunity is much more sophisticated. These troops, T and B cells, learn from previous invasions and mount enhanced and more specific defenses the second time around.

That's why it was a surprise when Ulrich von Andrian, an immunologist at Harvard Medical School in Boston, Massachusetts, noticed that mice without T or B cells were mounting a seemingly adaptive immune response equal to normal animals. His team had primed the immune systems of mice lacking T or B cells by painting a solution containing an antigen onto their backs. When that antigen was applied to their ears 5 days or 4 weeks later, the mice remembered it just as well as normal mice did: Their ears swelled with NK cells poised to fight it off. Mice that had a different kind of antigen applied to their ears did not show any swelling, suggesting that the response by the first group of mice was adaptive, the researchers report in the May issue of Nature Immunology. Von Andrian says the work has "called into question one of the fundamental paradigms of immunology"--the distinction between the innate and adaptive immune responses. He speculates that NK cells could be responsible for certain immune conditions, such as allergies, which can sometimes occur without the involvement of T or B cells.

"I think this is very exciting and very well carried out," says immunologist Philip Askenase of Yale University. "We all have to rethink things somehow." Immunologist Martin Flajnik of the University of Maryland School of Medicine in Baltimore agrees that linking NK cells with immune memory will shake up the field: "It's a heresy to suggest something like that." He suspects the cells may provide "a complementary or back up response" to the memory response normally carried out by T cells.

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