LA JOLLA, Calif., January 27, 2010 -- Investigators at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have discovered a new way the cell surface protein, CD44, helps specific T helper (Th1) cells develop immunologic memory. Linda Bradley, Ph.D., Bas Baaten, Ph.D., and colleagues determined that without CD44, Th1 cells died off during their initial immune response and were unable to generate immunologic memory. This is the first time scientists have identified this unique CD44 function on Th1 cells, making the protein a potential target to treat a variety of diseases. The study was published online on January 14 in the journal Immunity.
CD44, a protein found on many cell types throughout the body, binds to the glycan hyaluronic acid (HA) in the extracellular matrix. When T helper cells are activated by infection, they upregulate (increase the activity of) CD44. Though CD44 is a marker for these "experienced" cells, its function has remained elusive. T cells are important components in the body's defense against diseases and, as memory cells, provide immunity to subsequent infections.
"In various infections and autoimmune conditions, Th1 cells are often the bad guys," said Dr. Bradley. "They can contribute to disease by overproducing cytokines and are often responsible for the disease pathology. Our findings reveal an opportunity to harness CD44 to control this pathogenesis."
The Bradley laboratory used T cells lacking CD44 that recognized a protein fragment in the influenza virus. Noting that the T cells did not survive and were unable to generate immunologic memory, the laboratory determined that CD44 protected the cells from programmed cell death initiated by the Fas receptor. This protective effect was specific to a subset of T cells, the Th1 cells, and mediated by the PI 3 kinase pathway. The researchers also demonstrated that survival of the cells could be controlled by antibodies capable of modulating CD44 signaling.
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute (formerly Burnham Institute for Medical Research) is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The Institute ranks among the top independent research institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. From 1999 – 2009, Sanford-Burnham ranked #1 worldwide among all types of organizations in the fields of biology and biochemistry for the impact of its research publications, defined by citations per publication, according to the Institute for Scientific Information. According to government statistics, Sanford-Burnham ranks #2 nationally among all organizations in capital efficiency of generating patents, defined by number of patents issued per grant dollars awarded.
Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a nonprofit public benefit corporation. For more information, please visit www.sanford-burnham.org.
Journal
Immunity