Emory scientists track down immune sentinel cells with gene gun

Dendritic cells monitor foreign substances in the body and communicate whether they present a danger to the rest of the immune system. Emory immunologists have developed a sensitive method to detect and follow dendritic cells by marking them with a change in their DNA, and have discovered that they are more numerous and longer lived than other scientists had previously observed. Their research uses a gene gun, which shoots DNA into the skin using microscopic gold pellets, and could lead to a faster and simpler way to vaccinate against emerging diseases like West Nile virus, SARS, or hepatitis C.

The research was published online August 10, and will appear in the journal Nature Immunology in September. Lead authors are Sanjay Garg PhD, postdoctoral fellow, and Joshy Jacob, PhD assistant professor of microbiology and immunology at Emory University School of Medicine and the Yerkes National Primate Research Center. Both are members of the Emory Vaccine Center.

Dendritic cells, the security cameras of the immune system, derive their name from their finger-like projections. They continually capture external proteins, digest the proteins into fragments, and display those fragments on their surfaces. T cells, the police who watch the cameras, have the ability to examine the fragments on the dendritic cells’ surfaces and sound the alarm to the rest of the immune system if they determine that those fragments are dangerous. Although other kinds of cells also have the ability to present fragments of foreign proteins to the immune system, dendritic cells are the most proficient, and immunologists call them “professional” antigen-presenting cells.

Dendritic cells migrate between the skin, where one might expect to first encounter an intruder, and the lymph nodes, where T cells and other white blood cells congregate. Dr. Jacob’s group used transgenic mice engineered with a marker gene that can be easily detected by staining, but only when that gene is rearranged by an external signal. They shot the trigger signal – DNA encoding a specialized bacterial enzyme – into the skin of the mice. All the cells in the skin received the trigger signal, but only the dendritic cells migrated to the draining lymph nodes.

Dr. Jacob estimates that there are 1,000 dendritic cells for every square millimeter of skin. His group found that the number of dendritic cells that migrate into the lymph nodes is 100 times higher than previously thought, and that they live for two weeks, rather than just a few days. The scientists were able to observe the dendritic cells more accurately because the cells were marked permanently.

“This research resolves a long-standing puzzle,” says Dr. Jacob. “T cells that will recognize a given foreign protein are quite rare, so it was hard to imagine how the T cells and dendritic cells would ever meet. It is still remarkable that they do.”

The gene gun used to send the DNA into the skin uses gold pellets coated with the DNA. The pellets have a diameter of one micrometer and are driven with the force of a bullet. Dr. Jacob suggests that the DNA provides just enough of a signal to induce the dendritic cells, which are activated by inflammation or physical trauma, then migrate to the lymph nodes.

The gene gun could present an attractive alternative to conventional ways of making vaccines, Dr. Jacob notes. “Usually, you have to figure out how to grow a virus, then inactivate it so that it doesn’t actually cause an infection. This new methodology could take advantage of the immunizing capabilities of abundant, long-lived dendritic cells.”