Watching Natural Killers Work

Natural killer cells patrol the liver’s blood vessels, searching for disease-causing intruders. In the above micrograph of liver tissue, the cells are bright green.

Observing the journey of live immune cells in the liver for the first time in any laboratory, School of Medicine researchers have reported that these cells, which travel in the liver’s blood vessels and are called natural killer T (NKT) cells, move with surprising speed and agility.

NKT cells are the guardians of the liver. They patrol for foreign molecules on bacteria and viruses and, once they find the interlopers, alert the immune system to their presence. They are also thought to play a role in disposing of damaged cells and in scouting for tumors.

Led by Dan R. Littman, M.D., Ph.D., Professor of Pathology and a Howard Hughes Medical Institute investigator, and Michael L. Dustin, Ph.D., Associate Professor of Pathology, the study analyzed over a period of hours the movement of NKT cells and their response to foreign protein, or antigen, in mice.

The study revealed a number of surprises. First, the NKT cells did their work almost entirely within the blood vessels of the liver. Previously, conventional theory held that these cells were forced from the blood into the tissues, where they did their specialized work. Second, the NKT cells appeared to have the agility of a pro athlete. The cells moved and changed directions quickly, sometimes traveling against the direction of flowing blood, no mean feat.

The researchers were able to trace the movement of the cells by replacing a gene called CXCR6 with a gene for green fluorescent protein, which glows and makes the cells visible under a microscope. The researchers used a technique called intravital fluorescence microscope imaging to observe the behavior of the glowing cells in live mice.

The study showed that the cells were undisturbed by the rapid blood flow, latching onto the vessels, then moving in random patterns in search of infected cells. In another part of the study, the researchers injected a foreign molecule. Here again, the cells behaved like athletes. They abruptly stopped and remained still, signaling that they had found the antigen and were ready to undertake their next task of alerting the immune system.

Although it is still too early to know how these findings will apply to human diseases of the liver, Dr. Dustin says there is already “significant interest in studying the way in which NKT cells respond to antigen so that they might be used in tumor vaccines.”
The study was published in the April 5, 2005, issue of the Public Library of Science, an open-access, online journal.