ESTABLISHING peace between the warring immune systems of transplant patients and their donated organs could spare them from having to take powerful immunosuppressive drugs for the rest of their lives. Although this approach is in its early stages, it is looking very promising.
Researchers have been trying for years to find gentler ways of preventing rejection. Now a team led by Samuel Strober of Stanford University in California is using an ingenious strategy to prevent people who received kidney transplants from rejecting their new organs. To wean them off drugs, they gave the patients temporary transplants of cells belonging to the donor’s immune system, in order to train the recipient’s immune system to tolerate the organ.
Soon after the transplant operation, while the recipients were still on immunosuppressants, they began a course of antibody therapy and irradiation designed to kill off their most aggressive immune cells. The aim of this was to favour “peacekeeper” immune cells, which suppress attack from immune cells in the transplanted organ.
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The patients were then infused with haematopoietic stem cells (HSCs) from the donor. These cells come from our bone marrow and mature into blood or immune cells (91av 15 April 2000, p 11). In the transplant patients, they seeded themselves and produced new immune cells in the recipients’ weakened immune systems. This left the patients with a mixture of donor and recipient immune cells.
A few months after this treatment, the patients’ own immune systems regained complete control. But by then the hosts’ immune cells that had grown up in the presence of both immune systems had learned to tolerate both tissue types.
So far, four kidney transplant patients have been given the new treatment. The researchers were able to wean two of them off drugs completely after a year, while a third is on a reduced drug regime. The other rejected the donor cells immediately.
As Strober’s team report in the journal Transplantation later this month, one patient has had to restart drug therapy after four drug-free months, and the other drug-free patient may not be able to manage without immunosuppressant drugs for much longer.
But Strober says that even this is an improvement over current treatments. “We think this first patient will end up needing only one drug, rather than the three that are now commonly used,” he says.
Guido Silvestri, an immunologist at Emory University in Atlanta, Georgia, suspects that for the effects to be long lasting, the researchers will need to get the donor immune cells to persist for more than a few months. But he thinks the approach is well worth pursuing. “If this procedure proves to work reliably, it would be really terrific for transplant patients,” he says.
Strober’s team is considering increasing the dosage of HSCs in the next set of patients it tests. “Organ transplants are already a huge success,” says Strober. “We just want to get the same success without the drugs.”