Australian scientists have made a discovery that may one day remove the need for a lifetime of toxic immunosuppressive drugs after organ transplants.
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.