Lag-3 gene dampens immune responses by controlling regulatory T-cel...( The discovery that the Lag-3 gene acts ...)

The discovery that the Lag-3 gene acts as a brake to prevent immune system responses from running out of control solves a mystery that has puzzled researchers since the gene was discovered 14 years ago. A report on this discovery, from investigators at St. Jude Children's Research Hospital and The Johns Hopkins Kimmel Cancer Center, is published in the October issue of the journal Immunity.

The researchers solved the mystery of what Lag-3 does by showing that the gene permits so-called regulatory T cells to act as brakes on the immune system.

Regulatory T cells, which carry the Lag-3 protein on their surfaces, interfere with the action of effector T cells--the "warrior" cells that orchestrate attacks on specific targets in the body, such as cancer cells and microorganisms.

The finding could form the basis for new strategies for improving the efficacy of anti-cancer vaccines or preventing autoimmune diseases. Autoimmune diseases are those in which the immune system attacks specific tissues of a person's own body as if they were foreign matter. The researchers showed that the ability of regulatory T cells to control an attack by effector T cells is substantially prevented or eliminated in the absence of Lag-3.

Both the effector and regulatory cells arise from the same populations of cells, called CD4+ T lymphocytes, according to Dario A. A. Vignali, Ph.D., associate member of St. Jude Immunology. Vignali is senior author of the Immunity report.

The Lag-3 gene is activated in some of the CD4+ cells during an immune system response, turning them into regulatory cells that put the brakes on the activity of their fellow CD4+ T cells that are launching the attack.

"The braking action of regulatory T cells prevents the destructive effects of autoimmune diseases, such as diabetes type 1, which occurs when effector T cells mount an attack on the cells
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
19-Oct-2004

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