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TB Turns Up Immunity Surprise

Species of immune cells have 'memory' that helps them attack bacteria

THURSDAY, March 21, 2002 (HealthDayNews) -- A type of immune cell with a fraternity-like name could hold the key to a more effective vaccine against tuberculosis.

New research has revealed that gamma delta T cells have a "memory" for tuberculosis bacteria (TB). After being introduced to the germ, these cells will launch a massive attack against it when the two meet again.

"We were quite surprised in seeing this. We did not expect to see it at all," says Dr. Norman Letvin, a virologist at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston and a collaborator on the study.

"This changes how we have to think about what the usual immune response is to TB, and what we might be able to generate" with vaccines against the bug, he adds. A report on the findings appears in tomorrow's issue of Science.

TB is caused by Mycobacterium tuberculosis, a lung-loving germ that kills 2 million people a year globally, according to the World Health Organization.

In the United States, close surveillance and ready supplies of antibiotics have radically reduced the TB caseload. However, 16,000 Americans each year contract the infection, which in recent years has begun to show an alarming ability to resist the drugs used to treat it.

A vaccine against TB is available. Called BCG for short, the shot -- made from a non-fatal cow version of the TB germ -- has proved effective in children but is disappointing in adults.

The latest study could help scientists create inoculations that are more potent by specifically targeting gamma delta T cells, Letvin says.

The work centers on the two streams of immunity: the front-line defense system of cells that reacts to invading organisms; and the second group comes to battle after the initial response and helps finish off the infection.

Within the second group are cells considered to have "memories" for such microbes as bacteria or viruses. Once they've learned their lines, these actors are content to wait in the wings for their next cue -- in this case, a return of the offending organism.

Scientists have long thought that gamma delta T cells were effectively amnesiac and an important player in the innate immune response. Now, says Letvin, it turns out they may "straddle" the two defense systems.

Led by Dr. Zheng Chen, a TB researcher at Beth Israel Deaconess Medical Center, the Boston group looked closely at the immune response in macaque monkeys immunized with BCG, and in particular at gamma delta T cells.

Shortly after vaccination, the animals had a surge in gamma delta T cells. However, when the researchers re-injected the monkeys with vaccine, they saw a much more impressive spike.

In fact, the gamma delta T levels were twofold to ninefold higher after the second inoculation than after the first. The cells also lingered in the blood for up to seven months after the second shot.

Tests of the T cells proved that some were clones of the original family generated after the first vaccination, the researchers say.

Chen's group then exposed vaccinated and unvaccinated macaques to lethal TB. Both groups had jumps in gamma delta T cells.

While the unvaccinated animals died of the infection, the immunized ones remained healthy for a 2.5 month follow-up -- suggesting the priming was critical to survival.

What To Do: March 24 is World TB Day. For more on the killer disease, try the World Health Organization or the Centers for Disease Control and Prevention.

SOURCES: Norman Letvin, M.D., chief, viral pathogenesis, Beth Israel Deaconess Medical Center, and professor, Harvard Medical School, Boston; March 22, 2002, Science
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