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Researchers decipher chemical 'cross talk' that determines survival of immunecells

Molecular biologists at the University of California, San Francisco have deciphered a pattern of signals that spells life or death to each T cell of the immune system and may control the development of the body's natural defense arsenal.

When a virus, parasite or other pathogen invades a cell, the immune system's T cells recognize the enemy, and a potent chemical signal is triggered using a docking site known as the T cell receptor. The current research identifies a possible new role for this chemical message. The scientists suggest that the interplay between this signal and one produced by a hormone continually selects the T cell soldiers the body needs as it faces a changing cast of invaders. What controls this selection process has long puzzled biologists. The steroid hormone signal is normally present at low levels that fluctuate with daily rhythms, but stress can cause the hormone levels to spike. The new study may lead to a molecular understanding of how stress-induced hormone imbalance depresses immune system function, the scientists say. This imbalance sometimes leads the immune system to activate T cells that attack the body and cause autoimmune diseases.

The research was carried out to help clarify a larger question: how the cacophony of chemical messages streaming through a cell is ultimately "heard" as a single command to switch a gene on or off -- the fundamental unit of action in the cell.

"Signals from the environment, from hormones and many other sources are woven into a fabric," explains UCSF's Keith Yamamoto, PhD, professor and chair of molecular and cellular pharmacology. "It is the fabric that defines the state of the cell at any given time and determines whether or not genes are activated. We wanted to examine how different signals become integrated to produce instructions to the genetic machinery."

The scientists' findings are published in the June 20 issue of the Proceedings of the Nat
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
19-Jun-2000


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