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Study of Natural Killer T Cells in the Liver Yields Surprising Findings

 

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For the first time, the movement of natural killer T (NKT) cells in the liver has been observed. A team of researchers including Dan R. Littman, M.D., Ph.D., Michael L. Dustin, Ph.D., and Thomas O. Cameron, Ph.D., of New York University School of Medicine reported their groundbreaking research in the April 2005 issue of the Public Library of Science: Biology. The team was able to trace the movement of these cells in mice by replacing the CXCR6 gene with a green fluorescent protein and then viewing the resulting glowing cells by intravitan l fluorescence microscopic imaging. This study of liver cells resulted in several surprising findings including the observation for the first time that NKT cells conduct immunosurveillance almost entirely within the blood vessels of the liver. Previous studies suggested that the cells carried out their work in specialized compartments shielded from blood flow. Additionally, the researchers observed that the movement of the NKT cells in the quest to identify foreign cells, or antigens, was random and independent of the location of central veins or the direction of blood flow. The researchers also observed the reaction of NKT cells to the introduction of an antigen. When NKT cells recognize an antigen through T-cell antigen-receptor activation, they suddenly stopped roaming and were ready to undertake the next task of alerting the immune system. The gene that the researchers replaced (CXCR6) is known to be involved in cell movement. However, the extraction of this gene did not affect the movement of the NKT cells but did limit their life spans; suggesting that CXCR6 is somehow involved in the survival of NKT cells. The study’s findings of how NKT cells move and respond to antigens have important implications in understanding if NKT cells could be utilized in tumor vaccines. Drs. Littman and Dustin are members of the Institute’s Scientific Advisory Council and Dr. Dustin serves on the Fellowship Committee. Dr. Cameron is supported by a CRI Postdoctoral Fellowship. The full article can be viewed at:
http://biology.plosjournals.org/archive/1545-7885/3/4/pdf/10.1371_journal.pbio.0030113-L.pdf.