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.”
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