Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Chemical guidance of T cells leads to immunologic memory and long-term immunity

19.04.2006
In the latest issue of the journal Nature, scientists at the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) describe a new understanding about how long-term immunity works--findings that may lead to new ways of thinking about how to enhance certain immune responses and how to improve vaccines.

Led by immunologist Ronald Germain, M.D., Ph.D., the scientists took videos through a microscope to document what happens inside the lymph nodes of a living mouse shortly after a vaccination. The videos reveal that the movement of a specific type of immune cell known as a CD8+ T cell, also called a cytotoxic T cell, is not random as was previously thought, but instead is guided by chemical signals released from other cells.

Scientists have long recognized the importance of understanding how CD8+ T cells move through the lymph nodes and become activated. Once active, CD8+ T cells roam throughout the body destroying cells infected with bacteria or viruses--a process known as cell-mediated immunity. When these CD8+ T cells encounter an infected cell, they unleash a torrent of substances that poke holes in the cell’s membrane, chew up its proteins and ultimately cause it to die. They also produce molecules such as interferon-gamma that help activate other immune cells.

After they fight the initial infection, some of these CD8+ T cells remain in the circulation as memory cells, primed to fight if the host is re-infected with the same pathogen. Memory cells are key to vaccine strategies being studied for infectious agents such as HIV. But the CD8+ T cells can only become effective, long-lived memory cells after they encounter certain other cells in the lymph node that can activate them.

The new research, conducted largely by senior postdoctoral fellows Flora Castellino, M.D., and Alex Huang, M.D., Ph.D., with Dr. Germain’s guidance, shows that when CD8+ T cells enter the lymph node, a combination of specific physical and chemical cues guides them to sites where they receive activation signals. Specifically, two molecules known as chemokines help guide them toward the cells that release these activation signals.

"Understanding the processes whereby CD8+ T cells find their way in the lymph nodes is important because their activation is essential for eliminating infected cells and for providing, together with antibodies, long-lasting protection following vaccinations," says NIAID Director Anthony S. Fauci, M.D.

The body contains hundreds of millions of CD8+ T cells, but only a tiny fraction of them become activated during an infection. These are selected because each CD8+ T cell carries a unique surface protein called a T-cell receptor, which recognizes only specific antigens (pieces of virus or bacteria that trigger the immune response). During an infection, CD8+ T cells that recognize antigens from the infecting pathogen are activated. These antigen-specific CD8+ T cells expand into a large population of active clones, which then sweep through the body, hunting down and killing infected cells.

For CD8+ T-cell activation to occur in the lymph node, the cell must encounter its target antigen--but that antigen must be displayed on the surface of another immune system cell, called a dendritic cell. Usually a third type of cell, known as a "helper" T cell, must be involved as well. But how do the CD8+ T cells find the right dendritic cells presenting the specific antigen they need to see? Moreover, how do they find the particular dendritic cells that have been properly stimulated by helper T cells?

Dr. Germain and his colleagues determined that naïve CD8+ T cells do not wander aimlessly through the lymph node but instead are steered towards areas in which dendritic cells concentrate. Think of the lymph node as a large airport terminal and the CD8+ T cells as the arriving passengers, says Dr. Germain. If passengers know that limo drivers will meet them in the terminal, they will look for their drivers upon arrival. Rather than hoping to run into each other by chance, the drivers crowd around the arrival gates and hold up signs that the passengers can read from a distance.

Moreover, CD8+ T cells are chemically attracted to the cells that might activate them by the chemokines these other cells produce. Dr. Germain and his colleagues demonstrated that when CD8+ T cells enter the lymph nodes and detect a potential infection, they express receptors that allow them to detect and follow these chemokines.

The NIAID team also showed that when dendritic cells interact in specific fashion with helper T cells, the activated cell pair releases the chemokines CCL3 and CCL4. It is the combination of these two chemokines that the CD8+ T cells receive best as a signal, says Dr. Germain. By interfering with the action of these chemokines, he and his colleagues demonstrated that CD8+ T cells lost their ability to home in on the dendritic cells interacting with the helper T cells. The result was a marked impairment of memory cell generation.

These new findings not only provide insight into the fundamental behavior of the immune system, but also suggest that attention needs to be paid to chemokines and chemokine receptor function when designing new vaccine strategies and evaluating whether drugs targeting chemokines might have unanticipated effects on immune function.

Jason Socrates Bardi | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Life Sciences:

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>