scientists have long believed that humans and many other mammals have two types of immune systems: innate and adaptive. The former is driven by natural killer (NK) cells, which attack any cell it identifies as non-self, the latter by B and T cells that form long-term memories of particular antigens they meet so they are more prepared to fight that antigen in the future.
The NK cells are thought to form the first barrier of defense against any incoming pathogen, poking holes in the cells to kill them. Several years ago, researchers discovered that these NK cells may be able to form “memories” of previous antigen exposures and play a role in adaptive immunity, independent of B and T cells—in mice, at least.
Today (May 10), researchers report in Science Immunology the first observation of this NK function in humans, too.
“We were hopeful that if we can show that human natural killer cells also have this vaccine-induced or infection-induced specific memory of prior disease encounter that we could target them with vaccination, and perhaps improve vaccine development, for the protection of people from disease,” Silke Paust, an immunologist at the Scripps Research Institute and the senior author of the study, tells The Scientist.
“The previous studies that demonstrated there was pathogen-specific NK cell memory in animal models was a great surprise to the field. This [study] opens up the possibility that vaccination strategies could be developed to induce memory NK cells, along with memory T and B cells. If the findings of the current study . . . can be confirmed, this opens the door to additional means of vaccination,” Mary Markiewicz, an immunologist at Kansas University Medical Center who was not involved in the study, tells The Scientist in an email.
The study was conducted in two parts. First, the scientists decided on a mouse model that hosts a “humanized” immune system in which the animal’s immune cells are replaced with human ones. Then they exposed some of these mice to an HIV envelope vaccine and left others “naïve” as controls. Next, they harvested NK cells from the livers and spleens of the mice, cultured them separately, and exposed these cells to either another HIV envelope, an influenza virus, an inert protein, or nothing at all.
“If killing is antigen-specific, then the HIV-envelope–primed NK cells will only kill HIV-envelope–loaded targets, but none of the control targets,” says Paust. “This is what we saw.” NK cells from the mice exposed to the HIV antigen reacted when they encountered an HIV protein, but did not respond to the inactive protein, and showed a limited response to the influenza. NK cells from mice that hadn’t been exposed to the HIV envelope protein ignored or had a limited response to every exposure Paust’s team gave them….
