Professor Jonathan Sprent and Dr Kylie Webster from Sydney's Garvan Institute of Medical Research, in collaboration with colleagues, Dr Shane Grey and Stacey Walters, have successfully tested a method, in experimental mice, of adjusting the immune system for just long enough to receive a tissue transplant and accept it as 'self'. At no stage, during or after the procedure, is there any need for immunosuppressive drugs.
The results are now online in the current edition of the prestigious Journal of Experimental Medicine.
"Under normal circumstances, the body would attack a transplanted organ unless immunosuppressive drugs such as cyclosporin were given," said Sprent. "In this project, mice were given a substance, or 'complex', that altered their immune systems, so that they accepted transplanted cells as their own."
Sprent developed the 'complex' with Professor Charles Surh from California's Scripps Research Institute and Dr Onur Boyman, physician and Head of the Basic Immunology Unit at the University Hospital of Lausanne in Switzerland.
The complex combines a molecule, interleukin-2 (IL-2), with an antibody in order to stimulate immune cells known as T regulatory cells.
"In broad terms, IL-2 is a growth factor for T cells," explained Sprent. "My colleague Onur Boyman discovered that by combining IL-2 with different antibodies you can control its action, boosting specific populations of T cells, while subduing others. For this project we needed to boost the numbers of T regulatory cells."
"T regulatory cells quiet the immune system, subduing the body's killer T cells when it's time to stop fighting an infection."
"The other side of the coin is that a superabundance of T regulatory cells prevents killer T cells from functioning. And you wouldn't want to be without killer T cells for long because they fight infections and cancers."
"For this project, we boosted T regulatory cells temporarily, in a procedure that we believe might be very useful clinically, particularly for preventing rejection."
It was the task of postdoctoral researcher Kylie Webster, working with Stacey Walters, to see if she could make the T regulatory cell response work in a clinically realistic setting.
"We took normal, healthy mice, injected them for three consecutive days with the complex, then transplanted insulin-producing cells on the fourth day," said Kylie. "By the time of transplant there were huge numbers of T regulatory cells in their systems, making graft-destroying T cells ineffective."
"The numbers of T regulatory cells dropped over time, and the immune systems returned to normal in about two weeks. By that time 80% of the mice had accepted the grafts of insulin producing cells as their own."
"This acceptance rate is very high for transplantation, with mice normally rejecting grafts within 2-3 weeks."
"A graft is considered accepted if it's tolerated after 100 days. We took some mice out to 200-300 days, and not one of them rejected."
While cautious, Professor Sprent is very encouraged by the results.
"We have yet to determine exactly how the complex works. Once we do, I believe a clinical trial of this very non-toxic agent would be worthwhile."
"Our approach works well with pancreatic islets, or insulin-producing cells, but we have yet to try other clinically-relevant grafts such as kidneys and hearts, which are technically very difficult in mice," he said.
"I am also aware that effective approaches in mice do not necessarily give good results in humans because of subtle differences in the immune systems of mouse and man."
"Those provisos given, if we were able to duplicate this experiment in humans, it would fulfil the dream of everyone in the transplant field."
The Garvan Institute of Medical Research was founded in 1963. Initially a research department of St Vincent's Hospital in Sydney, it is now one of Australia's largest medical research institutions with nearly 500 scientists, students and support staff. Garvan's main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The Garvan's mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan's discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.
Alison Heather | EurekAlert!
Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
Foods of the future
15.08.2018 | Georg-August-Universität Göttingen
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences