LIAI Scientists Shed Light on Natural Killer T Cells Role in Fighting Disease; Research Could Lead to New Treatments for Bacterial Infections and Tumors.

SAN DIEGO -- Researchers at the La Jolla Institute for Allergy & Immunology (LIAI) have identified the bacteria, Sphingomonas, as containing a glycolipid which naturally triggers an immune response from the body's natural killer (NK) T cells. The finding sheds some light on the powerful, but little understood, workings of the NK T cells and will help scientists explore their possible use in fighting tumors and dangerous disease-causing bacteria.

In a paper, "Recognition of bacterial glycosphingolipids by natural killer T cells," to be published March 24 in the scientific journal Nature, Mitchell Kronenberg, Ph.D., and an international team of scientists working at the Scripps Research Institute, the Rockefeller University, New York University, and Kanto Gakuin University in Japan found that NK T cells, a type of white blood cell, exposed to the Sphingomonas bacteria's glycolipid quickly launched an immune assault to rid the body of the substance and bacteria carrying it.

Most white blood cells respond to foreign proteins to protect the body, but NKT cells are unique in that they respond to glycolipids, which are natural biochemicals made of linked fat and sugar. Previously, only one compound, developed by a pharmaceutical company in the 1990s, was known to activate the NK T cells. In a surprising twist, that compound was initially discovered in marine sponges. The compound was found to have anti-tumor activity and is currently in clinical trials for several tumor types. Because the NK T cells are known to be responsible for the tumor fighting mechanism induced by the marine sponge compound, and because their mechanism of action has been so mysterious, the NK T cells have generated increased research interest over the last several years.

Dr. Kronenberg and his lab have concentrated their studies on NK T cells since the cells were first discovered about 10 years ago. "They've been the subject of significant scientific interest because they initiate such a fast and vigorous immune response, which makes them very useful for anti-tumor responses and protection from infections," he said.

In particular, scientists wanted to know what substance would naturally activate the NK T cells. "Although the synthetic compound was useful for many studies, we wanted to know what substance would normally cause the NK T cells to produce an immune response, and it was not believable that marine sponges normally stimulate our immune system," said Dr. Kronenberg, who is also LIAI's President and Scientific Director. "We've found a bacteria in nature (Sphingomonas) that can activate these cells. We strongly suspect these cells may also have the capability of fighting other types of bacteria that can cause serious diseases. This is an exciting possibility that needs to be further explored." He added that the Sphingomonas bacteria are found throughout the environment but only rarely cause disease, perhaps because of the activity of NK T cells.

Kronenberg said the finding of a natural activator from bacteria will allow scientists to learn more about how NK T cells stimulate other cells of the immune system to fight infection and tumors.

About LIAI

Founded in 1988, the La Jolla Institute for Allergy and Immunology is a non-profit medical research center dedicated to increasing knowledge and improving human health through studies of the immune system. Scientists at the institute carry out research designed to understand and lead to the development of cures for cancer, allergy and asthma, infectious diseases, and autoimmune diseases such as diabetes, inflammatory bowel disease and arthritis. LIAI's research staff includes over 100 Ph.Ds.