U.S. Navy medical researchers have reached a significant milestone in medicine's search to find a way to prevent "mismatched" transplanted organs from being rejected.
U.S. Navy physicians Capt. David Harlan and Lt. Cmdr. Allan Kirk tested a novel medical therapy that seems to prevent the rejection of transplanted organs - even transplanted organs that are completely mismatched.
While the precise mechanism preventing the organ rejection remains unclear, the researcher's data suggests the immune system is "re-educated" to leave the transplanted organ alone.
Currently, individuals in need of a transplant must wait for an organ from a suitably matched donor.
After receiving the transplant, individuals must take anti-rejection medications for the rest of their lives to prevent the organ from being attacked by their own immune system and destroyed.
Anti-rejection drugs often have significant unpleasant side effects and increase individual's susceptibility to infections and tumors.
These drugs are also expensive.
As part of their research, the Navy team transplanted very mismatched kidneys into non-human primates and treated them with the new therapy for 28 days after the operation.
No other therapy, including the use of anti-rejection drugs, was administered.
Six months later, the primates are robust and suffering no significant side effects.
The short course of the therapy appears to be long-lasting, precluding the use of daily medication to prevent organ rejection.
The expected lifespan for primates with a mismatched kidney transplant that receives no treatment is less than ten days.
A summary of the team's research is in the Aug. 5 issue of the Proceedings of the National Academy of Science and on the Academy's Homepage at http://www.pnas.org.
Navy doctors routinely conduct basic, clinical and field research directly related to military requirements and operational needs.
This research is often done in partnership with other branches of the armed forces, universities and private industry, and has influenced the civilian and military practice of medicine.
Harlan and Kirk's research stems from earlier Navy work that suggests some immune responses could be turned "off" or "on" at will.
Controlling this off or on response are T lymphocytes, or T cells, which play a key role in the immune system by fending off infectious agents.
However, these T cells also recognize "invading" transplanted organs, and the immune response directed by the T cells ultimately leads to organ rejection.
This recent milestone was reached when the research team observed that T cells have two distinct "senses" to "sniff" out the intent of any invader, such as a transplanted organ.
One sense very specifically recognizes invaders.
This first sense can detect even subtle differences in tissues or organs.
However, simply recognizing an organ as an invader appears insufficient to alert T cells to call an all out attack.
For T cells to become alerted, they must not only recognize the invader as foreign, but must also have other T cell sensors simultaneously triggered.
These latter sensors are called "costimulatory receptors." The researchers' therapy allows the immune system to recognize the transplanted organ, but prevents costimulatory receptors from sounding the alarm to attack the invading organ.
According to the United Network for Organ Sharing, which tracks organ transplant data, almost 4,000 Americans died in 1996 as they waited for a compatible organ donor.
Many thousands more have decreased quality of life while they wait for an organ match or suffer from anti-rejection drug side effects.
Harlan and Kirk believe that in addition to preventing organ transplant rejection, their research may provide help for immune system illnesses ranging from the relatively innocuous but annoying hay fever to severe and potentially life threatening illnesses such as multiple sclerosis and lupus.
Harlan and Kirk work at the Naval Medical Research Institute (NMRI) in Bethesda, Md.
Others collaborating on this project include Dr. Tom Davis and researchers at NMRI, transplant surgeon Dr. Stuart Knechtle and his colleagues at the University of Wisconsin - Madison, and scientists from the Navy's civilian partner organizations.
For more information contact, Jan Davis at the Department of the Navy Bureau of Medicine and Surgery Public Affairs Office at (202) 762-3223.