By reprogramming cells in the immune system, a team of scientists led by a Howard Hughes Medical Institute (HHMI) international research scholar has found a way to boost production of natural killer T cells, with long-term potential for fighting diseases in which the body attacks its own cells.

Natural killer T (NKT) cells maintain the immune system's balance between destruction and tolerance, a mechanism that is off kilter in autoimmune diseases such as type 1 diabetes and irritable bowel disease.

"If we can regulate the level of NKT cells, we have a chance to slow down the process of type 1 diabetes," said team leader Lszl Nagy, HHMI international research scholar and a molecular biologist at the Research Center for Molecular Medicine, University of Debrecen, Hungary. He and colleagues from the Research Center collaborated with a scientist from Albert Einstein College of Medicine in New York to do the series of experiments, which was published in the July 2004 issue of the journal Immunity.

After finding that a transcription factor called PPAR-gamma is expressed in dendritic cells--the immune system's first responders--Nagy and colleagues used a drug called rosiglitazone to increase PPAR-gamma activity. The additional PPAR-gamma activity prompted immature dendritic cells to develop into a form that could activate NKT cells specifically.

"Everyone knew that dendritic cells are derived from monocytes, and we knew there were different kinds of dendritic cells," Nagy said. "But nobody knew the regulatory events that drove dendritic cells to differentiation. We described a pathway to make dendritic cells with a special phenotype that includes NKT cell induction."

Dendritic cells wait in peripheral tissue, such as the skin, ready to engulf foreign invaders or dying cells. Once they take up fragments of these cells, known as antigens, they migrate to the lymph nodes, where they prime T cells to mount a specific imm
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Contact: Jennifer Donovan
donovanj@hhmi.org
301-215-8859
Howard Hughes Medical Institute
20-Jul-2004

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