September 15, 2003

Researchers mark cells with golden ‘gene gun’

Quinn Eastman

Emory immunologists have developed a sensitive method to detect and
follow dendritic cells—which monitor foreign substances in the body and communicate with the immune system—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 appears in the September issue of Nature Immunology, and its lead authors are Sanjay Garg, postdoctoral fellow, and Joshy Jacob, assistant professor of microbiology and immunology at 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 them 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 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; 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. 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 skin cells received the trigger signal, but only the dendritic cells migrated to the draining lymph nodes.

Jacob estimated there are 1,000 dendritic cells for every square millimeter of skin. His group found the number of dendritic cells that migrate into the lymph nodes is 100 times higher than previously thought, and the cells 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,” said 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 shoots gold pellets coated with the DNA. The pellets have a diameter of one micrometer and are driven with the force of a bullet. Jacob suggested that the DNA provides just enough of a signal to induce the dendritic cells, which are activated by inflammation or physical trauma, to migrate to the lymph nodes. This could present an attractive alternative to conventional ways of making vaccines, he said.

“Usually you have to figure out how to grow a virus, then inactivate it so that it doesn’t actually cause an infection,” Jacob said. “This new methodology could take advantage of the immunizing capabilities of abundant, long-lived dendritic cells.”