Teaching T Cells: Researchers nab cells that build the thymus (Immunology; Cancer)
Authors: Leslie Mitch 
Published: August 2003

Like a lot of youngsters, immature T cells don't find their calling until they leave home--for the thymus. There, thymus cells push them into a career in defense and teach them to spot the enemy. Now researchers have corralled the precursors of the instructor cells. Transplants of these primordial cells might rejuvenate the gutted immune systems of older cancer patients, which lack the capacity for self-renewal.
The thymus, a spongy organ above the heart, serves as a military academy for infection-fighting T cells. Schooled by cells there, the immune cadets learn which foreign molecules to attack; any traitors that might turn on the body's own tissues are drummed out. Like many other parts of our bodies, the thymus shrivels with age, graduating fewer and fewer T cells. The slowdown in T cell production probably causes few troubles for a healthy elderly person, says Jason Gill, an immunologist at Monash University in Melbourne, Australia. But it is dire for the many older folks with cancer whose immune systems are hammered by chemotherapy. A young person's immune system rebounds, but the trickle of new T cells from a withered thymus isn't sufficient to rebuild immunity, leaving elderly cancer patients particularly vulnerable to infection. Researchers hoped to fire up the immune system by cultivating the thymus cells that nurture T cells, but they slammed into an obstacle. No one knew whether the cells shared a common origin or were a "grab bag," says immunologist Beth Jamieson of the University of California, Los Angeles.
To find out, Gill and colleagues went hunting for the cells that build a thymus in mice. Through a systematic search, researchers in the same lab had identified a marker protein that might characterize these ancestral cells. In the new work, Gill and colleagues found that cells toting this marker are abundant early in embryonic development but their numbers dwindle later on, which suggested that they could be the elusive progenitors. To confirm the possibility, the team transplanted bundles of the cells into the kidneys--where many blood vessels can nurture new tissue--of adolescent mice. After 8 weeks, the transplants formed functioning minithymuses bustling with normal T cells. "They were lovely--plump and white, as you'd expect a thymus to be," says Gill. The results suggest that a single group of cells, carrying the marker protein, spawns the thymus.
The findings might lead to a therapeutic strategy that could save many lives, says immunologist Daniel Douek of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. Infusions of precursor cells won't give the average 60-year-old the immune system of a teenager, he says. But such a treatment could help older cancer patients regenerate their defenses and might also save people who are infected with HIV or have undergone bone marrow transplants. First, researchers must track down the human versions of the primordial cells, which means finding a comparable marker protein. Gill and colleagues have already started the search. "Everything indicates the cells are there; it's just a matter of fishing them out," says Gill.
--Mitch Leslie

J. Gill, M. Malin, G. Höllander, R. Boyd, Generation of a complete thymic microenvironment by MTS24
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thymic epithelial cells.
Nat. Immunol.
, 17 June 2002 [e-pub ahead of print].
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