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Natural Killers Could Lead to New Hepatitis Treatments

Researchers have discovered that natural killer T (NKT) cells, the immune system's sentinels, patrol the labyrinthine blood vessels of the liver for invaders or signs of tissue damage and demonstrate a dogged behavior not seen before in other T cells.

The new studies show that NKT cells crawl along vessel walls, even upstream against blood flow. They halt only when they receive a chemical signal to unleash an immune-system assault on marauding microbes, other invaders or damaged tissue.

The findings offer a new way of thinking about this important class of immune cell, which is responsible for the inflammation and cell death in the liver due to hepatitis. Hepatitis can be a reaction to viruses, parasites such as malaria or other infections. Learning to “call off?the NKT cell's pursuit and attack could offer a treatment for hepatitis and associated complications.

The researchers, led by Dan Littman, a Howard Hughes Medical Institute investigator at New York University (NYU) School of Medicine, published their findings online on April 5, 2005, in the Public Library of Science Biology. Lead authors on the paper were Frederick Geissman in Littman's laboratory and Thomas Cameron in the laboratory of co-author Michael L. Dustin, also of NYU. Other co-authors were from the La Jolla Institute for Allergy and Immunology and Millennium Pharmaceuticals in Cambridge, Mass.

Although it was known that NKT cells were more prevalent in the liver than in any other organ, said Littman, it was not known how they accomplish the Herculean task of immune surveillance in the liver. The liver detoxifies and removes waste products from the blood. Inside the liver, vascular passages, or “sinusoids,?are filled with a witches' brew of nutrients, toxins, proteins, lipids and other chemicals. Thus, immune guardians that patrol the liver must tolerate many foreign molecules, yet respond readily to infection.

“It wasn't clear how NKT cells survey (tissue), or
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Source:Howard Hughes Medical Center


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