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From
•>>May 2005
Ronald N. Germain answers
a few questions about this month's fast moving front in the
field of Immunology.
Field: Immunology
Article: Dynamic imaging of T cell-dendritic cell interactions in lymph nodes
Authors: Stoll, S;Delon, J;Brotz,
TM;Germain, RN
Journal: SCIENCE, 296: (5574) 1873-1876, JUN 7 2002
Addresses: NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
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 Why
do you think your paper is highly cited?
Until the publication of this paper and the accompanying papers
in Science in 2002, immunologists have had to imagine how
the critical cell-cell interactions that give rise to adaptive
immunity take place within lymphoid tissues. They had to use
static data from stained sections of frozen or fixed samples to
construct a mental picture of the highly dynamic events involved
in activation of lymphocytes by foreign material (antigen). This
paper and two others published in the same issue of Science
provided the first "moving pictures" of the behavior of
different cell types within lymphoid tissues. Our work in
particular also helped resolve a contentious issue, namely how
long a T cell interacts with an antigen-bearing dendritic cell.
This is thought to be a crucial parameter in the control of T
lymphocyte differentiation and could not be determined in a
physiologic tissue context by any other available technique.
Does
it describe a new discovery or a new methodology that’s useful to
others?
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"This
paper and two others published in the same issue
of Science provided the first "moving
pictures" of the behavior of different cell
types within lymphoid tissues. Our work in
particular also helped resolve a contentious
issue, namely how long a T cell interacts with an
antigen-bearing dendritic cell." |
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This paper and the co-published papers from Miller et al.
and Bousso et al. described the adaptation of advanced
microscopy techniques (confocal and 2-photon imaging) to the imaging
of intact tissues. These constituted entirely new applications for
these microscopy methods to investigating immune system function.
Could
you summarize the significance of your paper in layman’s terms?
The following is the text from a news release from the NIH
describing the paper and its significance.
"For years, scientists studying the immune system have
based their observations on snapshots of isolated cells and
tissues. Now, thanks to emerging technologies, researchers can
have front-row seats to the dance of immune cells occurring
within living tissues. New research, reported in three papers in
the June 7 issue of the journal Science, for the first
time visualizes the behavior of immune cells and their targets
in intact lymph nodes. The publications open the door to
important new discoveries that were not possible using previous
techniques. "It is ‘The Immune System: The Movie’,"
says Ronald Germain, M.D., Ph.D., deputy chief of the laboratory
of immunology at the National Institute of Allergy and
Infectious Diseases (NIAID) and a principal author of one of the
studies. "We can now follow individual T cells within
intact tissues to observe how they behave and interact with
other cells as immune responses develop." Much of our
current understanding of the interplay among immune cells and
their targets has been inferred from looking at chemically
stained cells in thin slices of tissues observed under a
microscope. Video microscopy has been used to observe the
movement of cells, but its use has been limited to small samples
grown in culture. In the three new papers, researchers use two
types of microscopes that can scan through a thick sample and
limit their focus to living cells lying deep within the lymph
nodes, the structures in the body where immune cells are
activated in response to microbial invaders or other signals.
According to Dr. Germain, the new technique will permit
investigators to explore questions they previously could not
clearly address: for
example, how long do T cells remain in contact with their target
cells, when do the T cells divide, and where do different types
of T cells go once they have been activated? The study by Dr.
Germain and his colleagues examined how T cells interact with
dendritic cells within lymph nodes. Dendritic cells are key
components of early immune responses which mop up invading
microbes, display fragments of those microbes to T cells, and
help trigger the T cells to respond. Contrary to what some
researchers previously believed, Dr. Germain’s team, with the
support of NIAID’s biological imaging facility, showed that
individual T cells remain in contact with dendritic cells for
prolonged periods. After that time, the T cells become
activated, separate from the dendritic cells, and migrate away.
The study provides a new glimpse into key steps in early immune
responses and paves the way for future work on T-cell
activation."
These advances open the way to more definitive studies of the
processes involved in triggering immune cells that play key roles
in host defense against infectious agents and tumors and that go
astray to produce allergic diseases and autoimmunity. They add new
spatial and time information that complement the results from
other types of experiments seeking to understand how to generate
better vaccines or ameliorate damaging immune responses that lead
to diseases such as asthma or multiple sclerosis.
How
did you become involved in this research?
I am an avid photographer and have always thought about
biologic processes in terms of "mental images." It
struck me years ago that actually creating "real" moving
pictures of the events in immune responses would greatly enhance
our understanding of how the immune system actually does its job.
After several tries, I finally convinced a postdoctoral fellow in
my laboratory that the risk involved in trying to develop the
needed techniques was worth taking. Dr. Sabine Stoll did an
incredible job in getting what is a very difficult procedure to
actually work and an even more remarkable job in collecting and
interpreting the images she obtained to draw key biological
conclusions that have now been confirmed by several other
laboratories.
Ronald N. Germain, M.D., Ph.D
Deputy Chief, Laboratory of Immunology and
Chief, Lymphocyte Biology Section, NIAID, NIH, DHHS
Bethesda, MD, USA
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