Scientists at New York University School of Medicine viewing the actual journey of immune cells in the liver have found that these cells travel in the liver's blood vessels with surprising speed and agility.
It is the first time that the movement of live immune cells called natural killer T (NKT) cells has been seen in the liver, according to a study published in the April 5, 2005, issue of the Public Library of Science, an open-access, online journal.
NKT cells are the guardians of the liver. They patrol the liver for foreign molecules on bacteria and viruses and once they find the interlopers, they 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., PhD., 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. "This is the first example of a system in which a cell's surveillance for antigen is intravascular rather than within a tissue," says Dr. Littman.
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 on to the vessels, then moving in random patterns in search of infected cells. "Despite the force of the directional blood flow, the cells were able to hold their own, moving and changing direction, sometimes passing each other within a single blood vessel," explains Dr. Dustin.
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.