NEWS: BYU researchers target substance that helps immune system kick in

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Article Last Updated: 11/16/2004 02:18 AM

BYU researchers target substance that helps immune system kick in

By Greg Lavine

The Salt Lake Tribune

In the quest to better understand how the immune system works, researchers

in Utah and Illinois appear to have uncovered a key substance that helps

fight problems ranging from diabetes to cancer.

Studying mice and human cells, scientists at Brigham Young University and

other institutions around the world uncovered a substance that activates

natural killer T cells. These specialized T cells are key in determining

whether the body's immune system attacks a health threat or ramps down its

response.

Savage, a BYU chemist, said the missing key is an antigen, a

molecular substance that serves as a signal for the immune system. When this

antigen is absent, the body creates few or no natural killer T cells.

" They really determine what type of immune responses are produced, "

Savage said of the T cells. The paper, authored in part by Savage and

scientists from the University of Chicago, appears in the online version of

the journal Science.

Knowing what this antigen looks like should allow scientists to determine

where and how it is produced in the human body, he said.

When natural killer T cells are absent, a host of autoimmune diseases can

occur, including Type I diabetes, lupus, multiple sclerosis and rheumatoid

arthritis. In these medical problems, the body's immune system attacks

itself.

The natural killer T cells direct other types of T cells to attack or

ignore an unwanted visitor. Without these directors, it seems that T cells

can rage out of control and create unneeded immune responses.

A link between natural killer T cells and some autoimmune diseases could

lead pharmaceutical companies to target future treatments toward stimulating

or suppressing the production of natural killer T cells, Savage said.

Albert Bendelac, a University of Chicago immunologist involved in the

study, said there remains some debate over whether a lack of natural killer

T cells causes autoimmune problems. He said it is a promising idea, but that

more research is needed.

In addition to autoimmune problems, the work on natural killer T cells

also holds potential for other health issues.

" They seem to be involved in a variety of anti-cancer activities, "

Bendelac said.

When cancer first appears in the body, it contains substances that prompt

the body's immune system to produce natural killer T cells. A proper immune

system response can eliminate the attacker before it takes hold and spreads,

Bendelac said.

But when the immune system creates no natural killer T cells, the cancer

can grow unchecked.

Researchers believed the trigger, or antigen, to create natural killer T

cells was a lipid, which is a type of molecule. It remained unclear which of

dozens of lipids was involved.

University of Chicago scientists studied laboratory mice that had been

bred to have trouble producing a variety of lipids from a class known as

glycolipids. Each group of mice was missing a different glycolipid than

another group.

The group unable to produce natural killer T cells provided the clue

about which missing glycolipid was key to the immune malfunction.

" It was just some great detective work at Chicago, " Savage said.

University of Chicago researcher Dapeng Zhou served as lead author of the

study.

BYU's role in the study was to synthesize, or manufacture, this

glycolipid, which was then tested in mouse and human cells. In each case,

the glycolipid made natural killer T cells more active, Bendelac said.

" This current study by Dr. Bendelac and his colleagues provides the most

compelling information so far on the identity of the [antigen trigger that

creates natural killer T cells], " said Porcelli, a researcher at

Harvard University, Cambridge, Mass., who was not part of the study.

Medical researchers have been interested in learning more about the

mechanics of natural killer T cells and how they affect the immune system,

said Dale Godfrey, an immunologist at the University of Melbourne,

Australia, who was not involved in the study.

" A major goal in this field of research has been to identify the

molecular signals that are involved in switching these cells on, " Godfrey

said. " The study by Zhou and colleagues offers an important piece to this

puzzle. "

If further research confirms the role of the glycolipid as the main key

to switching on and off natural killer T cell production, the molecule would

provide a tempting target for future drug therapy in cancer and autoimmune

diseases, he said.

BYU graduate students Ning Yin and Ying Gao were involved in the study.

BYU and the University of Chicago worked with the following groups: the

Scripps Research Institute, La Jolla, Calif,; the National Institutes of

Health, Bethesda, Md.; Gateborg University, Gateborg, Sweden; the Chinese

Academy of Sciences, Beijing, China and the University of New Hampshire,

Durham, N.H.

http://www.sltrib.com/healthscience/ci_2454055