T cells 'hunt' parasites like predators stalk prey, veterinary researchers find

A cross-disciplinary team of veterinary researchers and physics analysts at the University of Pennsylvania have arrived at a somewhat surprising finding: T cells, a key immune system component, track parasites using a movement strategy similar to that of sharks, monkeys and other predators when hunting prey.

The research was led by Christopher Hunter, professor and chair of the pathobiology department in Penn's School of Veterinary Medicine, and Andrea Liu, professor of physics in the school's department of physics and astronomy. Penn Vet postdoctoral researcher Tajie Harris and physics graduate student Edward Banigan also played leading roles.

The study was conducted in mice infected with Toxoplasma gondii, which were used as a model to learn how T cell movement in the brain affects the body's ability to control T. gondii infection.

According to information released by the University of Pennsylvania, the researchers sought to pinpoint the exact movement patterns of individual T cells in living tissue from T. gondii-infected mice using multi-photon imaging, a technique that uses a powerful microscope to display living tissues in three dimensions in real time.

Using this technique the Penn researchers found that, contrary to what immunologists have assumed, the T cells showed no directed motion. That's where the statistical physics expertise of Liu and Banigan came in. "After some work we managed to find a model that fit the tracks beautifully," Liu says.

That model is known as a Lévy walk. This "walk," or a mathematical path, tends to have many short "steps" and occasional long "runs." The model was not fully consistent with the data, however. "Rather, I had to look at variations on the Lévy walk model," Banigan says, because the researchers also observed that the T cells paused between steps and runs. Like the movements of the cells, the pauses were usually short but occasionally long.

Hunter likens the model to a strategy a person might employ to find misplaced keys in the house. "When you lose your keys, how do you go about looking for them?" he says. "You look in one place for a while, then move to another place and look there."

"What that leads to is a much more efficient way of finding things," Liu says. That makes sense for T cells, which have to locate sparsely distributed parasites in a sea of mostly normal tissue.

T cells are not alone in employing a Lévy-type strategy to find their targets. Several animal predators move in a similar way—with many short-distance movements interspersed with occasional longer-distance moves—to find their prey. The strategy seems particularly common among marine predators, including sharks, tuna, zooplankton, sea turtles and penguins, though terrestrial species like spider monkeys and honeybees may use the same approach to locate rare resources.

This parallel with animal predators also makes sense because parasites, like prey species, have evolved to evade detection. "Many pathogens know how to hide, so T cells are not able to move directly to their target," Hunter says. "The T cell actually needs to go into an area and then see if there's anything there."

The model is also relevant to cancer and other immune-mediated diseases, Hunter notes. "Instead of looking for a parasite, these T cells could be looking for a cancer cell," he says. By knowing what controls T cell movement, "you might be able to devise strategies to make the T cells more efficient."

With this new insight into immune-cell movement, researchers may be able to create more accurate models of immune-system function, which may in turn inform novel approaches to combat diseases from cancer and arthritis to HIV/AIDS.