News ID: 121901
Published: 0312 GMT July 08, 2015

Organ transplant rejection may not be permanent

Organ transplant rejection may not be permanent

Rejection of transplanted organs in hosts that were previously tolerant may not be permanent, report scientists from the University of Chicago. Using a mouse model of cardiac transplantation, they found that immune tolerance can spontaneously recover after an infection-triggered rejection event, and that hosts can accept subsequent transplants as soon as a week after.

According to Live Science‎, this process depends on regulatory T-cells — a component of the immune system that acts as a 'brake' for other immune cells. The findings support inducing immune tolerance as a viable strategy to achieve life-long transplant survival, pyroenergen.com reported.

"Transplantation tolerance appears to be a resilient and persistent state, even though it can be transiently overcome," said Anita Chong, PhD, professor of transplantation surgery at the University of Chicago and co-senior author of the study. "Our results change the paradigm that immune memory of a transplant rejection is invariably permanent."

Chong and her colleagues have previously shown in mice that certain bacterial infections can disrupt tolerance and trigger rejection of an otherwise stable transplant. As they further studied this phenomenon, they made a surprising observation. Infection-triggered rejection caused the number of immune cells that target a transplant to spike in tolerant mice as expected. But they were dramatically reduced seven days post-rejection. This ran counter to rejection in non-tolerant recipients, where these cells remain at elevated levels.

To identify the explanation for this observation, the team grafted a heart into the abdominal cavity of experimental mice and induced immune tolerance. After two months of stable tolerance, the researchers triggered rejection via infection with Listeria bacteria, which caused the transplant to fail. They then grafted a second heart from a genetically identical donor as the first, a week after rejection of the initial graft. This second transplant was readily accepted and remained fully functional over the study period. A second set of experiments, in which a second heart was grafted roughly a month after rejection to give potential immune memory more time to develop, showed similar long-term acceptance.

The team discovered that regulatory T cells (Tregs) —  a type of white blood cell that regulates the immune response by suppressing the activity of other immune cells — were required for the restoration of tolerance. When they depleted Tregs in a group of mice one day before the transplantation of the second heart, the newly transplanted organ was rejected. This suggested that Tregs act as a 'brake' that prevents other immune cells from targeting and rejecting the second transplant.

 

   
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Resource: pyroenergen.com
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