Figure 1: A newborn mouse (top) expressing the color-swapping Kaede protein in its cells. When the mouse is exposed to violet light for the indicated times (bottom), its green cells turn red, and can be tracked as they move through the body.
Reproduced from Ref. 1 © 2008 by The National Academy of Sciences of the USA
Immune cells migrate throughout the body to monitor different organs and rapidly respond to invading pathogens. Now it is possible to monitor immune cell transport in a line of genetically engineered mice that was created by a team of researchers led by Osami Kanagawa at the RIKEN Research Center for Allergy and Immunology in Yokohama, and including Yoshihiro Miwa at the University of Tsukuba, and Atsushi Miyawaki at the RIKEN Brain Science Institute in Wako.
The mice were modified to express a new color-shifting fluorescent protein called ‘Kaede’ in all their cells. Normally, the Kaede protein glows green. But when cells expressing the Kaede protein are exposed to violet light, it glows red (Fig. 1), without any effect on cellular function.
To track the cells, the researchers made a small incision in the skin near the groin of the mice to expose the inguinal lymph node to violet light, which caused all of the Kaede protein in the cells to become red. This effectively flagged the origin of the red cells.
Using this technique, the researchers determined the speed of transport of different types of lymph node immune cells—T cells, B cells, and dendritic cells—to different tissues and organs in the body. They also located where the cells would migrate. The different types of immune cells migrated from place to place at different speeds, and migrated to different locations, including the blood, other lymph nodes, the spleen, bone marrow, liver and lung.
Many of the inguinal lymph node cells migrated to the axillary lymph node in the armpit, suggesting that these two lymph nodes may be directly connected to each other through a lymphatic vessel. Kanagawa and colleagues confirmed this by injecting blue dye into the inguinal lymph node, which was rapidly detected in the axillary lymph node.
The researchers also were able to observe the migration of immune cells from the skin, an organ that is not part of the immune system. When they exposed the skin to violet light, the immune cells found there migrated into a nearby lymph node.
Future experiments could use the mice expressing the Kaede protein to monitor cell movement during autoimmune disease induction, and during immune responses to pathogens. “We recently made another mouse line, in which the Kaede protein can be expressed in a tissue-specific manner, and we would like to use these mice to study when and where the initial immune response starts,” says Kanagawa.