French scientists develop new strategy to stop transplant rejection
French researchers have developed a new therapy which successfully prevents transplant rejection while avoiding many of the side effects of the drugs currently given to transplant patients.
The results, carried out by a team led by Joost van Meerwijk of the French National Institute for Health and Medical Research (INSERM) are published in the journal Nature Medicine.
Controlling the body's extremely strong immune reaction to transplanted organs remains a major challenge for modern medicine. Immunosuppressant drugs have improved survival in the first year after transplant by effectively preventing acute rejection of the new organ. However, they are less effective at preventing chronic rejection which arises much later and affects a significant number of transplant patients. Furthermore, as immunosuppressants block the entire immune system, patients taking them are particularly prone to opportunistic infections and the development of certain cancers.
In healthy people, special cells called regulatory T lymphocytes (Tregs) ensure that the body's immune system does not turn against itself. For a number of years, Professor Van Meerwijk and his colleagues have been investigating ways of taking advantage of this regulatory role of Tregs in transplant medicine.
In 2004, they showed that regulatory T lymphocytes effectively inhibited the rejection of a bone marrow transplant in mice. However, until now they have proven less effective at preventing the rejection of skin and heart transplants. Undeterred, the researchers designed a new experiment based on the fact that a bone marrow transplant makes subsequent organ transplants easier.
The first step of the newly designed protocol involved placing regulatory T lymphocytes in a culture with cells from the organ donor. Over a two week period, the T cells effectively 'learnt' to recognise the organ which was to be transplanted.
The scientists then carried out a double transplant on the recipient mouse, involving both bone marrow and an organ (either skin or heart). At the same time, the mice received an injection of Tregs from the culture.
The experiment was a success, with neither acute nor chronic rejection of either transplant taking place. 'In conclusion, we have demonstrated that adequately prestimulated Tregs can be used to protect skin and cardiac allografts from acute and chronic rejection,' the scientists write.
'This cellular therapy has two major advantages: an effective prevention of chronic rejection and a specificity of immunosuppression towards the transplanted organ, thereby avoiding a large number of undesirable side effects,' commented Professor Van Meerwijk.
The next step is to find out if the same procedure could be as effective in humans. The researchers note that the induction of tolerance to organs or tissues should be feasible using their protocol or a modified version of it. Furthermore, with some adjustments it could also be used to induce tolerance to transplants taken from dead organ donors.
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