Investigators at St.
Jude Children's Research Hospital have discovered a new signaling molecule
that prevents immune responses from running amok and damaging the body. The
finding could lead to the development of new treatments for cancer, using
vaccines; for autoimmune diseases, such as Type 1 diabetes; and for
inflammatory diseases, such as inflammatory bowel disease and asthma.
The St. Jude team discovered that specialized immune lymphocytes called
regulatory T cells release a protein complex composed of two proteins
called Ebi3 and Il12a. This complex acts like a brake on the activity of
the aggressive immune cells called effector T lymphocytes. The discovery is
important because the manipulation of regulatory T cells is a key goal of
immunotherapy. A report on this discovery appears in the journal "Nature"
Nov. 22, 2007.
The newly recognized protein complex is one of a large group of
signaling molecules called cytokines that cells use to communicate with
each other. Since the immune system cytokines are called interleukins, the
St. Jude team named this protein interleukin-35 (IL-35). Most cytokines
stimulate immune system cells; however, IL-35 is one of the few signaling
molecules known to inhibit immune system activity.
"The maximal suppressive function of regulatory T cells depends on
IL-35, so blocking IL-35 activity might reduce the ability of T cells to
block anti-tumor immune responses," said Dario Vignali, Ph.D., associate
member in the St. Jude Department of Immunology, and the paper's senior
author. "Treatments that block IL-35 activity may make anti-cancer vaccines
more effective and provide new therapeutic opportunities for autoimmune and
inflammatory diseases."
"Our findings suggest that controlling levels of IL-35 in patients
might one day allow clinicians to dial the immune response up or down
depending on the needs of the patient," said Lauren Collison, Ph.D., a
postdoctoral fellow in Vignali's laboratory who contributed significantly
to the project. Collison is the paper's first author.
Other authors of the paper include Creg Workman, Kelli Boyd, Yao Wang,
Kate Vignali and Richard Cross (St. Jude); Timothy Kuo and Richard Blumberg
(Harvard Medical School; Boston); and David Sehy (eBioscience, San Diego).
This work was supported by the National Institutes of Health (to D.V.
and R.B.), a Cancer Center Support Grant and ALSAC (to D.V.), a St. Jude
Gephardt Postdoctoral Fellowship and an NIH Individual National Research
Service Award (to L.C.), and the American Liver Foundation (to T.K.).
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for
its pioneering work in finding cures and saving children with cancer and
other catastrophic diseases. Founded by late entertainer Danny Thomas and
based in Memphis, Tenn., St. Jude freely shares its discoveries with
scientific and medical communities around the world. No family ever pays
for treatments not covered by insurance, and families without insurance are
never asked to pay. St. Jude is financially supported by ALSAC, its
fundraising organization. For more information, please visit
stjude.
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