Ongoing research at Emory University directed at achieving true immune tolerance without the need for immunosuppression continues to attract attention.
The November 22 issue of The Lancet (1997;350:1526) describes recent developments in a strategy reported in Nature last year by Christian P. Larsen, MD, and Thomas C. Pearson, MD, associate professors of surgery at Emory. In laboratory mice, the investigators used reagents to block the molecule pairs CD28-B7 and CD40-gp39; the molecules stimulate the action of T cells, which help the immune system to fight off transplanted tissues.
"Larsen and Pearson found that if they treated mice to block these two signaling pathways at the time of transplant, they could maintain grafts of transplanted tissue for long periods of time without using any other immunosuppressive medicines," Emory explained in a press release.
Although the transplanted tissues were tolerated for much longer periods with the double blocking strategy, the grafts eventually were rejected. However, according to Emory, recent experiments combining other therapies with the blocking mechanisms suggest that the researchers may be closer to "achieving true tolerance."
The investigators also are hopeful that other recently completed experiments using the blocking strategy in xenotransplantation can pave the way for xenotransplantation in humans.
Larsen and Pearson's theory has been extended to monkeys. In August, Allan D. Kirk, MD, PhD, and colleagues at the Naval Medical Research Institute in Bethesda, Md., reported that mismatched kidney grafts survived long-term in monkeys (Proc Natl Acad Sci USA 1997:94;8789-8794). According to The Lancet, Kirk and coworkers are testing newer costimulation blockers with more specific binding.
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