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Natural Killers Could Lead to New Hepatitis Treatments

even if they survey at all,?said Littman. To visualize the activity of NKT cells in the liver, Geissman used mice in which NKT cells were tagged with a fluorescent marker. This was accomplished by replacing the gene encoding a characteristic NKT cell surface receptor called CXCR6 with the gene for green fluorescent protein. Although the CXCR6 receptor is known to be central to the function of NKT cells, its overall role was not known, said Littman.

Working with Geissman, Cameron adapted a technique called intravital fluorescence microscopy that enabled them to observe in real time the behavior of the tagged cells in the livers of mice.

“The startling discovery was that these NKT cells just move within the sinusoids intravascularly,?said Littman. By contrast, he said, immune cells in the lymph nodes and spleen perform their surveillance ensconced within specialized compartments shielded from the turmoil of the bloodstream. “In this case, it looks like NKT cells are doing their surveillance from within the vessels,?he said.

The observations revealed that the NKT cells crawl randomly within the sinusoids, even against blood flow, passing one another and even changing direction, said Littman. “It is very different from the kind of classical mechanism of lymphocytes rolling through vessels with the blood flow and when they are activated coming to a stop and then crossing through vessel walls in response to a signal.?/p>

The researchers observed that the roving NKT cells stopped their movement when alerted by a foreign protein, called an antigen, “We think this is a reflection of their normal function of searching for antigen,?said Littman. “Whenever there is detection of antigen reflecting some kind of damage or local infection, the cell would stop in the vicinity of that signal and provide cytokine signals that would attract other inflammatory cells that destroy the invading microorganism and may also facilitate repair of the damage.?/p> '"/>

Source:Howard Hughes Medical Center


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