Current issue
Immunity in action
Rockefeller scientists capture
the first-ever live images of
immune system dendritic
cells at work
BY LYNN LOVE
If the immune system is an army, the lymph
nodes are its field command centers. Located at pivotal traffic
points throughout the body, they coordinate information sent back
from immune system cells that circulate along the body’s
periphery.
Now, in a series of experiments that has
caused scientists to rethink some of their basic beliefs about how
the cells of the immune system communicate with one another,
Rockefeller’s Michel Nussenzweig, along with Michael
Dustin of NYU Medical School, and colleagues have used genetic
techniques and fluorescent microscopy to penetrate deep inside lymph
nodes and visualize the activities of specialized components of the
immune system called dendritic cells.
The work, which was published in the December
issue of Nature Immunology, provides the research
community’s first
view, in real time, of the live actions of a network of dendritic
cells that spend their entire lifespan inside the body’s
lymph nodes.
Dendritic cells were discovered by Rockefeller
scientists Ralph Steinman and Zanvil Cohn in 1973, and they play a
special role in protecting the body from microbes and other
potential threats, such as cancerous tumors. The dendritic
cells’ long, spindly arms extend and retract in order to
detect antigens. Once foreign material, or antigens, are detected,
dendritic cells migrating throughout the body typically travel to
the lymph nodes to use those same spindly arms, called processes, to
inform other immune cells, the white blood cells called T and B
cells, to take action.
But in addition to migratory dendritic cells,
scientists now say there’s a network of dendritic cells that
never leave the lymph nodes, and serve primarily to teach T and B
cells what the body’s own tissues look like so that they will
be safe in the event of an immune system emergency.
To visualize these stationary dendritic cells,
the research team created laboratory mice genetically modified so
that their dendritic cells produce a yellow fluorescent protein. The protein, coupled with a
microscopic imaging technique that excites the fluorescent
molecules with infrared light, creates perfect conditions for
studying molecular activity in living systems.
“This imaging study has never been done
before,” says co-first author Randall Lindquist, a
Rockefeller University graduate student in Nussenzweig’s
Laboratory of Molecular Immunology. “All of the other live
microscopy experiments looking at dendritic cells in lymph nodes
used cells that came from other sources and that were labeled with
fluorescent dye.” Lindquist and his colleagues’ imaging
technique preserves the immune system’s natural conditions to
the fullest extent possible, and most closely represents how the
immune system really works.
“It surprised us to see that this
entirely different population of dendritic cells inside lymph nodes
form what looks like a stationary network,” says Lindquist.
“The network dendritic cells are just sitting there waving
their processes. They’re not migrating.”
The much-studied mobile population of
dendritic cells seems to interact with the stationary population,
says Lindquist. In a related set of experiments, the researchers
showed that transiting, mature dendritic cells can and do join the
network, and they likely share their information across the
network.
“Being able to watch dendritic cells in
their natural state is valuable,” says Lindquist. If this
network is teaching other immune cells to recognize, or tolerate,
the body’s own tissues significant medical advances in the
treatment of cancer and autoimmune diseases such as lupus may
follow.
Already other research teams around the
country are following in the Rockefeller-NYU team’s
footsteps, and Nussenzweig, the university’s Sherman
Fairchild Professor, predicts many new dendritic cell insights will
emerge from noninvasive live-imaging techniques, such as the system
he and his colleagues have developed.
Lindquist, Nussenzweig and their colleagues,
too, are pursuing many new experiments based on what they’ve
already learned. “The next thing we’d like to
determine,” says Lindquist, “is how the network
dendritic cells interact with T cells under conditions that induce
tolerance or active immunity.”
January 28, 2005
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