Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists develop a novel strategy to help prevent transplant rejection

05.12.2003


A study led by Imperial College London has shown for the first time it is possible to help prevent organ rejection using a novel strategy that redirects the body’s immune response instead of suppressing it.



Writing in the Journal of Clinical Investigation today, researchers from the University of Cambridge, the University of Edinburgh, Lorantis Ltd and Imperial demonstrate that it is possible in mice to alter whether T white blood cells specialise to attack foreign tissue and thus cause rejection, or instead become part of the body’s peacekeeping force, which patrols the body, defending against attack.

Unlike current therapies, which leave patients vulnerable to infection by inducing non-specific immunosuppression, this new approach targets a key cellular signal known as Notch, which the researchers found acts as a gatekeeper by governing how immune cells specialise.


Results show that exposing the mice to a combination of the Notch signal and material from the donor two weeks in advance of transplantation stimulates an immune response and significantly increases transplant acceptance from 20 to up to 80 days.

Professor Maggie Dallman of Imperial’s Centre for Molecular Microbiology and Infection, and senior author of the paper, said:
"Today, even with extensive efforts to find the best possible immunological match between donor and recipient, organ transplantation resigns the recipient to a lifetime of powerful immunosuppressive drugs that have many unwanted side effects.

"Increasingly organ transplants in the case of kidneys, liver or lung tissue occur between living relatives so you know in advance who the donor and recipient are. Our strategy opens up the possibility of offering gentler postoperative therapy by redirecting the recipient’s immune system in advance of the transplant."

T cells are the arm of the immune system that patrol the body, seeking out and destroying diseased cells. There are two key types of T cells: T helper cells, which stimulate immune response, and T suppressor cells that put the brakes on it.

To test Notch’s role in organ rejection the researchers transplanted a heart into the abdomen of a mouse. The heart was connected by two major vessels to the recipients blood supply so it had a beat but did not pump blood round the body.

When the mice were exposed to the pre-treatment regime, the length of time the heart was accepted for increased by up to four fold. This effect was found to be specific to pre-exposure to the foreign tissue that was subsequently transplanted and dependent on the presence of T suppressor cells at the time of transplantation.

"Results indicate that the presence of the Notch signal appears to promote the expansion of T suppressor cells, and provoke a corresponding decrease in T helper cells," says Professor Dallman.

"The key role that T suppressor cells play in preventing organ rejection is also supported by the observation that depleting their numbers at the time of transplantation reverses the effects of pre-treatment, and reducing the number of T helper cell numbers enhance transplant survival."

Further investigation indicates the mice did eventually reject the hearts because the T suppressor cells induced in these experiments only prevented one method of rejection.

"Rejection can occur by two mechanisms," explains Professor Dallman. "Either directly, where immune cells recognise transplant tissue as foreign, or indirectly through communication with other immune cells. The approach we used only targeted the direct method of rejection, but we believe that our approach will be equally effective against the indirect route when appropriately applied."

Professor Dallman added: "While the crucial role that Notch signalling plays in development has been well documented, scientists are only just beginning to examine its role in regulating the immune system.

"Now, we have an understanding of the key differences Notch signalling can impose on T-cell dependent immunity and, we believe that our approach may also be effective in the treatment of autoimmune diseases like diabetes or MS and in the treatment of allergy."

The clinical and commercial rights to this broad new approach to changing immune responses have been assigned to Lorantis Ltd. The company recently announced that it has raised £25 million from private equity venture funds to develop products based on Notch signalling in transplantation, autoimmune disease and allergy.

Dr. Mark Bodmer, Chief Executive Officer of Lorantis Ltd, comments:
"The ability to selectively suppress the immune response to disease-causing antigens has the potential for immunotherapy by ’reverse’ vaccination, where we down-regulate an unwanted response to an antigen rather than stimulate it. This represents a huge opportunity to benefit patients and build our company. We have been extremely pleased to be able to get strong financial support to move this important academic innovation into industry."

This work was funded by Lorantis Ltd, the European Union, the Wellcome Trust, the Medical Research Council and the British Heart Foundation.

Judith H Moore | EurekAlert!
Further information:
http://www.ic.ac.uk/

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

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 >>>