|Researchers Discover New Battleground for Viruses and Immune Cells|
Finding Should Aid Those Developing Anti-Virus Vaccines
Vaccines have led to many of the world's greatest public
health triumphs, but many deadly viruses, such as HIV, still elude
the best efforts of scientists to develop effective vaccines against
them. An improved understanding of how the immune system operates
during a viral infection is critical to designing successful anti-virus
vaccines. Scientists from the National Institute of Allergy and
Infectious Diseases (NIAID), part of the National Institutes of
Health (NIH), have added an important dimension to this knowledge.
Focusing on mouse lymph nodes — bean-shaped organs that contain
a variety of immune cells and are distributed throughout the body — the
researchers discovered that immune cells confront viruses just
inside of the lymph node and not deep within these organs as previously
thought. The study, led by Jonathan Yewdell, M.D., Ph.D., chief
of the NIAID Cellular Biology Section and his NIAID colleague,
Heather Hickman, Ph.D., is described in a report online in Nature
The results are significant, the authors say, as they observed
in detail the interaction of viruses and immune cells inside a
living organism, in this case, mice. Combining expertise from disciplines
such as imaging, immunology, virology and other specialties, the
scientists first extracted and then purified specific T cells — killer
T cells — from mice. Killer T cells, which attack and kill infected
or cancerous cells, are major weapons in the immune system arsenal.
The scientists labeled the T cells with a fluorescent marker, injected
them back into the mice, and then infected the animals with vaccinia
virus, the virus used to make smallpox vaccine, engineered to express
a brilliantly colored protein.
Using a multiphoton microscope, a highly specialized microscope
that enables scientists to peer into a living organism, the scientists
could now look into the lymph nodes of the infected mice and see
that the viruses had infected cells just inside the lymph node
surface, triggering a swarm of T cells. These virus-specific T
cells form an elaborate and dynamic communications network that
activates them to divide and travel to the site of viral infection,
where they kill virus-infected cells.
"A key challenge in viral vaccine research is developing
strategies for immunizing against lethal viruses such as HIV that
have eluded the standard vaccine approaches," notes Dr. Yewdell. "We
have contributed a page to the handbook of understanding how to
rationally design vaccines to elicit a T-cell response." According
to the NIAID team, pinpointing where in the lymph node immune cells
fight the virus should help efforts to design effective anti-virus
NIAID is a component of the National Institutes of Health. NIAID
supports basic and applied research to prevent, diagnose and treat
infectious diseases such as HIV/AIDS and other sexually transmitted
infections, influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research on basic immunology,
transplantation and immune-related disorders, including autoimmune
diseases, asthma and allergies.
News releases, fact sheets and other NIAID-related materials
are available on the NIAID Web site at http://www.niaid.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
H Hickman et al. Direct priming of antiviral CD8+ T cells in the peripheral interfollicular region of lymph nodes. Nature Immunology DOI: 10.1038/ni1557 (2008).