Two proteins may help transplants.

Doctors who perform organ transplants get used to rejection. The recipient's natural defenses identify new tissues and attack them as they would any other foreign body Several drugs help counteract this onslaught, but they must be taken indefinitely by most patients, and often produce side effects. The body's defenses are suppressed, exposing patients to opportunistic infection by harmful invaders.

Now, a preliminary study in rhesus monkeys highlights two proteins that together can block rejection, even after medication stops, without locking up the whole immune system in the process.

In a dozen monkeys that had undergone kidney transplants from unrelated rhesus monkeys, the two proteins--CTLA4-Ig and 5C8--even reversed organ rejection once it had started, a team led by researchers at the University of Wisconsin-Madison reports in the Aug. 5 Proceedings of the National Academy of Sciences. The proteins are genetically engineered antibodies.

Researchers gave eight of the monkeys one or both of the proteins. The four monkeys that received no drugs rejected their transplants within 8 days.

Two monkeys that received equal doses of the two proteins for 4 weeks after surgery remained healthy beyond 150 days. Of two monkeys that received the same amount of the drugs in just 2 weeks, one died of unrelated diseases and the other rejected the transplanted kidney after roughly 100 days.

The two that received only CTLA4-Ig rejected the new organ within a month. The other two, which got only 5C8, rejected it after about 100 days.

After rejecting the transplant, the two monkeys that had received only 5C8 and the survivor that had been given the short course of both drugs received a second round of their respective drug regimens--and they recovered.

"The ability to reverse acute rejection was an unexpected finding," says Stuart J. Knechtle, a University of Wisconsin immunologist who worked on the study. The researchers were also surprised that 5C8 worked alone. Knechtle suspects that a second wave of immune system cells attacks the new tissue after the first month, making an extended regimen more effective.

The researchers don't know how the two proteins work to limit rejection. John J. Fung, who has used them in rodent studies at the University of Pittsburgh, says they may create an environment in which the immune system's T cells cannot become activated.

The monkeys that survived remained free of opportunistic infection. To mimic potential use in humans, the researchers now plan to give the proteins to monkeys that have already taken standard antirejection drugs, Knechtle says.