Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

’Genetic switch’ proves two mechanisms exist by which immune system cells differentiate

07.10.2003


The thymus, a once overlooked glandular structure just behind the top of the sternum, has gained increasing attention from scientists in the past two decades because it is where disease-fighting T-cells mature.



Especially in AIDS patients, T-cell count is a relative indicator of the body’s ability to fight disease. Until recently, however, researchers have understood little about how T-cells are generated.

Now, thanks to what a researcher at the University of Georgia calls a "lucky lab accident," a new "genetic switch" involved in T-cell maturation has been discovered. The finding, published today in Nature Immunology, could help find ways to "restart" T-cell production in older adults and victims of disease such as AIDS.


"What this means is that when these cells grow or differentiate, it is a two-stage process," said Dr. Nancy Manley, an assistant professor of genetics at UGA and an adjunct assistant professor at the Medical College of Georgia. "This puts us a step closer to producing important epithelial cells from the thymus in the lab, though we are a long way yet from being able to turn the production of T-cells back on in the human body."

Co-authors on the research paper were Brian Condie and Dong-ming Su of the University of Georgia and Won-jong Oh and Samuel Navarre of the Medical College of Georgia. The work is supported by a grant by the National Institutes of Health.

The primary vehicle for studying T-cell development in the laboratory is the mouse. Researchers have known for years that a gene called nude--which causes mice to grow without hair of any kind--is also involved in immune response. Thus, mice with the nude gene have no T-cells and as a result have virtually no means of fighting off disease unless they are raised and live in germ-free environments.

In what Manley calls a "lucky accident," the team, in trying to produce a mouse with a fluorescent protein under control of the nude gene, came up with something entirely unexpected. The mouse, with the nude gene absent, should have been born completely without hair. Instead, its hair came in and grew normally.

At first, the team though that a mistake had been made--that the gene had simply not been deleted in this mouse. But when they looked at the thymus in these mice, they found, to their surprise, that it was abnormal but still made some T-cells.

Manley instantly knew that the lab mistake was a golden opportunity. It showed for the first time that the role of the nude gene in T-cell production is far more complicated than previously thought.

The specific cells in the thymus required for T-cell maturation are thymic epithelial cells (TECs). In the mutant nude mouse, these TECs fail to grow and mature, so no T-cells are made. But in the mutant made in Manley’s lab, the thymus did produce T-cells, although in greatly reduced numbers.

It turned out that the initiation and progression of TEC growth are genetically separable functions in the new mutant mouse. In addition, the team provided the first genetic evidence that an already-known process called "crosstalk" is needed for the growth of the thymic epithelial cells.

"Normal nude mice never even start to develop T-cells, because the TE cells remain immature," said Manley. "These mutants are now telling us how TE cell differentiation occurs. This is the first nude mutant that can produce partially functional TE cells and as a result can also make some T-cells. Now we have to figure out how it happens."

The practical applications of the research are considerable. The action of the thymus in producing mature disease-fighting T-cells peaks in a person’s mid-teens and then slowly erodes. This is one reason why older people and babies are frequently sickened by or die from diseases that cause little harm to those from their teenage years to midlife.

Likewise, certain diseases can kill off T-cells, making the body vulnerable to a host of infectious diseases, almost as if their bodies had suddenly grown very old. Armed with new evidence about the action of thymic epithelial cells, researchers may one day be able to selectively turn on T-cell production--making numerous disease far less virulent or even extending life.

These results also have further significance in light of recent reports identifying a putative TEC progenitor or "stem" cell. While identification of stem cell populations for specific tissues is a critical step, it is also important to know how to control their growth and development, to allow the production of specific mature cell types in the lab.

"A real problem so far has been that we just can’t make T-cells in the lab," said Manley. "But now at least we have better tools for understanding how they are made in the body, even though the entire process remains unclear. We can say that now we are closer than ever to being able to make thymic epithelial cells in the lab."

With more than 100 of the mutant mice now flourishing in germ-free conditions in Manley’s lab, the work continues

Kim Carlyle | EurekAlert!
Further information:
http://www.uga.edu/

More articles from Life Sciences:

nachricht Bacteria as pacemaker for the intestine
22.11.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Corporate coworking as a driver of innovation

22.11.2017 | Business and Finance

PPPL scientists deliver new high-resolution diagnostic to national laser facility

22.11.2017 | Physics and Astronomy

Quantum optics allows us to abandon expensive lasers in spectroscopy

22.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>