Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune cells fighting chronic infections become progressively 'exhausted,' ineffective

22.10.2007
Potential interventions to restore disease-fighting capability outlined

A new study of immune cells battling a chronic viral infection shows that the cells, called T cells, become exhausted by the fight in specific ways, undergoing profound changes that make them progressively less effective over time.

The findings also point to interventions that would reverse the changes, suggesting that novel therapies could be developed to reinvigorate T cells that become depleted in their struggle against a virus. Alternatively, strategies that would intentionally trigger the immune-dampening mechanisms explored in the study could prove useful in countering autoimmune disorders in which the immune system is inappropriately activated.

Although the experiments were conducted in mice, the problem of T-cell exhaustion has also been identified in HIV, hepatitis B, and hepatitis C infections in humans, as well as some cancers, such as melanoma. A report on the study results appears in the current issue of Immunity, published online October 18.

“We knew that T cells responding to chronic infections become progressively compromised in many of their functional properties,” says E. John Wherry, Ph.D., an assistant professor in the Immunology Program at The Wistar Institute and lead author on the Immunity study. “Put simply, the T cells become exhausted as time passes. What we wanted to learn in our study was what the specific problems were with these cells and whether their depleted state could be reversed.”

Using a technique called gene-expression profiling, Wherry and his colleagues identified 490 genes whose activity in T cells is altered during a chronic viral infection. Closer study at different time points using a 22-gene subset of the larger group of genes provided molecular signatures of progressive T-cell exhaustion. Only a few changes in the activity of the 22 genes were seen at the end of the first week of infection, increasing to 9 differences at two weeks, 18 differences at one month, and 21 differences at two months. At the end of two months, T cells contending with a chronic infection were sluggish metabolically and immunologically unresponsive to stimulus.

One gene identified as playing a central role in this process is called PD-1, which codes for an inhibitory receptor on the surface of the T cells. By blocking PD-1 in vivo, the researchers found they could alleviate T-cell exhaustion, get more functional T cells, and control the infection better.

“Blocking this one pathway partially reverses T-cell exhaustion in some settings, suggesting that we may be able to intervene to reinvigorate depleted immune cells,” says Wherry. “The T cells undergo many changes during chronic infections, however, so that it will be important to learn how to treat them for multiple problems.”

Wherry notes that the mechanisms involved in T-cell exhaustion also have important upsides.

“The flip side of this process is that the immune system has developed an effective way to turn off its response to a stimulus – which is exactly what one wants to do in the case of autoimmunity,” he says.

He points out, too, that the energy outlay during the acute phase of the immune system’s response to an infection is enormous – and fundamentally unsustainable.

“In the first week of an immune response to a virus, T cells can divide every four to six hours, as fast as any other mammalian cell at any time during development,” Wherry says. “In terms of their rate of division, T cells are in the same category as cells in the earliest stages of embryonic development. The energy involved in doing this is extraordinary, and the body can’t keep that up for an extended period of time.”

Franklin Hoke | EurekAlert!
Further information:
http://www.wistar.org

Further reports about: Chronic T cells T-cell Wherry become exhaustion progressively

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>