"Long before it's in the papers"
June 02, 2012

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Immune system cells found to hunt like real predators

May 30, 2012
Courtesy of the University of Pennsylvania
and World Science staff

T cell­s—com­po­nents of our im­mune sys­tems that find and kill path­o­gens—move much like pred­a­to­ry an­i­mals as they do so, a study has found.

The in­sight should help sci­en­tists de­vise bet­ter mod­els of im­mune-system func­tion, pos­sibly help­ing to fight dis­eases from can­cer to AIDS to ar­thri­tis, said scient­ists at the Uni­vers­ity of Penn­syl­va­ni­a who con­ducted the re­search.

The stu­dy, pub­lished in the lat­est is­sue of the re­search jour­nal Na­ture, was con­ducted in mice in­fected with the par­a­site Tox­o­plas­ma gon­dii. This single-celled path­o­gen is a com­mon cause of in­fec­tion in hu­mans and an­i­mals; as much as a third of the world’s popula­t­ion has a dor­mant form of it in the brain, though it’s harm­less in most cases.

The re­search­ers used the in­fected mice to learn how the move­ment of T cells in the brain af­fects the body’s abil­ity to con­trol the in­fec­tion. The in­ves­ti­ga­tors tracked the move­ment pat­terns of T cells in tis­sue from T. gon­dii-in­fected mice us­ing mul­ti­-photon im­ag­ing, a tech­nique based on a re­fined, pow­er­ful mi­cro­scope that can dis­play liv­ing tis­sues in three di­men­sions in real time. 

Sci­en­tists haven’t thought that much about T cell move­ment pat­terns, but to the ex­tent that they have, many as­sumed T cells moved in a highly di­rect­ed way to­ward their prey, the Penn re­search­ers said. This turned out to be wrong, they claim. For a time, the ac­tu­al move­ment pat­terns were per­plex­ing, but the Penn group even­tu­ally con­clud­ed that the cells’ move­ment was a var­i­ant of a known pat­tern called a Lévy walk. 

This “walk” char­ac­ter­izes the hunt­ing pat­terns of many preda­tors, and is really a type of path that fea­tures many short “steps” and oc­ca­sion­al long “runs.” Such a strat­e­gy seems par­tic­u­larly com­mon among ma­rine preda­tors, in­clud­ing tu­na, sharks, zo­o­plank­ton, sea tur­tles and pen­guins, the sci­en­tists said, though land an­i­mals like spi­der mon­keys and hon­ey­bees may use the same ap­proach to find rare re­sources.

The T-cells seemed to put their own twist on the Lévy walk by tak­ing pauses be­tween steps and runs. These pauses—like the move­ments them­selves—were usu­ally short but some­times long.

Chris­to­pher Hunt­er, a co-sen­ior au­thor of the stu­dy, likened the strat­e­gy to the way some­one might find mis­placed keys in the house. “How do you go about look­ing for them? You look in one place for a while, then move to an­oth­er place and look there,” he said. “What that leads to is a much more ef­fi­cient way of find­ing things,” added An­drea Liu, the oth­er sen­ior au­thor.

The strat­e­gy makes sense for T cells, which have to lo­cate sparsely dis­trib­ut­ed par­a­sites in a sea of mostly nor­mal tis­sue, the sci­en­tists added. The par­al­lel with preda­tors makes sense, they said, be­cause par­a­sites act like prey: they have evolved to evade de­tec­tion. “Many path­o­gens know how to hide, so T cells are not able to move di­rectly to their tar­get,” Hunt­er said. “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 not­ed. “In­stead of look­ing for a par­a­site, these T cells could be look­ing for a can­cer cel­l,” he said. By know­ing what con­trols T cell move­ment, “you might be able to de­vise strate­gies to make the T cells more ef­fi­cient at find­ing those cells.”

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T cells—components of our immune systems that find and kill pathogens—move much like predatory animals as they do so, a study has found. The insight should help scientists devise better models of immune-system function, possibly helping to fight diseases from cancer to AIDS to arthritis, said researchers at the University of Pennsylvania who conducted the research. The study, published in the latest issue of the research journal Nature, was conducted in mice infected with the parasite Toxoplasma gondii. This single-celled pathogen is a common cause of infection in humans and animals; as much as a third of the world’s population has a dormant form of it in the brain, though it’s harmless in most cases. The researchers used the infected mice to learn how the movement of T cells in the brain affects the body’s ability to control the infection. The investigators tracked the movement patterns of T cells in tissue from T. gondii-infected mice using multi-photon imaging, a technique based on a refined, powerful microscope that can display living tissues in three dimensions in real time. Scientists haven’t thought that much about T cell movement patterns, but to the extent that they have, many assumed T cells moved in a highly directed way toward their prey, the Penn researchers said. This turned out to be wrong, they claim. For a time, the actual movement patterns were perplexing, but the Penn group eventually concluded that the cells’ movement was a variant of a known pattern called a Lévy walk. This “walk” characterizes the hunting patterns of many predators, and is really a type of path that features many short “steps” and occasional long “runs.” Such a strategy seems particularly common among marine predators, including tuna, sharks, zooplankton, sea turtles and penguins, the scientists said, though land animals like spider monkeys and honeybees may use the same approach to find rare resources. The T-cells put their own twist on the Lévy walk by taking pauses between steps and runs, pauses that—like the movements themselves—were usually short but sometimes long. Christopher Hunter, a co-senior author of the study, likened the strategy to the way someone might find misplaced keys in the house. “How do you go about looking for them? You look in one place for a while, then move to another place and look there,” he said. “What that leads to is a much more efficient way of finding things,” added Andrea Liu, the other senior author. The strategy makes sense for T cells, which have to locate sparsely distributed parasites in a sea of mostly normal tissue, the scientists added. The parallel with predators makes sense, they said, because parasites act like prey: they have evolved to evade detection. “Many pathogens know how to hide, so T cells are not able to move directly to their target,” Hunter said. “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 noted. “Instead of looking for a parasite, these T cells could be looking for a cancer cell,” he said. By knowing what controls T cell movement, “you might be able to devise strategies to make the T cells more efficient at finding those cells.”