Also, rapamycin's effects depend on the dose -- too high a dose will inhibit all T cells without regard to what type they are, he says.
Araki and Ahmed teamed up with Christian Larsen, MD, PhD, director of the Emory Transplant Center and chair of the Department of Surgery, to show that rapamycin had similar effects in rhesus macaques infected with vaccinia virus as in mice. That research was conducted at Emory's Yerkes National Primate Research Center.
Rapamycin, also called sirolimus, was approved by the FDA in 1999 for use after kidney transplants. It was discovered in a soil sample from Easter Island, whose Polynesian name is Rapa Nui.
Transplant patients usually don't take rapamycin by itself, so rapamycin's paradoxical effects may have been masked by other drugs, Larsen says.
For transplant patients, memory T cells can play a role in graft rejection, but they can also protect against infections.
"We are appreciating more and more that memory T cells respond differently to interventions than nave T cells and we have to pay close attention to the situation of the individual patient," Larsen says.
Scientists at the Emory Vaccine Center continue to study how T cells decide whether to become memory cells, because of their importance in maintaining the immune response against chronic infections such as HIV and hepatitis C.
The effects of rapamycin were seen even if Araki gave animals rapamycin only for a week after the infection began, suggesting that the beginning of the infection was when T cells were deciding whether or not to become memory cells.
By using an inhibitory technique (RNA interference) on the genes known to be targeted by rapamycin, Araki was able to show that rapamycin is acting on the CD8 T cells and not on other cells with which they interact.
|Contact: Holly Korschun|