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 The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

nachricht A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg

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: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>