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Arthur T Knackerbracket has processed the following story:

Organ transplant recipients take life-long immunosuppressive drugs to prevent their bodies from mounting an immune response against the donated organ, yet a substantial number of them still reject the organs. A new study by researchers from the University of Chicago shows that transplant recipients also mount an immune response against commensal bacteria in the organ graft, adding to the immune response against the genetic makeup of the tissue and reducing the effectiveness of immunosuppressive drugs.

The study, published today in the Journal of Clinical Investigation, also shows that this anti-microbial immune response can be triggered by immune cell memory of previous encounters with bacteria, further complicating the body's ability to accept a lifesaving new organ.

"Before, we thought the reason why transplanted organs in humans are less easily accepted than in sheltered laboratory animals is that humans can have immune memory responses that cross-react on the cells of the organ, and memory responses are more difficult to suppress with drugs than naïve responses," said Maria-Luisa Alegre, MD, PhD, Professor of Medicine at UChicago and senior author of the study. "Now, we see that it's not only memory cells that recognize the organ itself that are the problem, but also memory responses that recognize bacteria in the organ."

The success of organ transplants depends on the type of organ. Lungs and small intestines are notoriously difficult to transplant and have shorter survival times. Statistics show that within five years of surgery, 41% of lung and 54% of intestinal transplant recipients rejected their grafts, compared to organs like kidneys (just 27% rejection) and hearts (23%). One hypothesis was that lungs and intestines, but not kidneys and hearts, are exposed to microbes from the air and digestive system and that the organ recipients were mounting immune responses not only to the organs but also to the microbes in those organs.

[...] Most importantly, when they transplanted mice with skin grafts that were genetically different and colonized with bacteria -- simulating the scenario like most human organ transplants -- they saw that immunosuppressive drugs that prolonged transplant survival in naïve mice did not work in mice with anti-bacterial memory.

"That explains why when you transplant a lung or intestine, patients do less well and have to receive higher levels of immunosuppression than when you transplant sterile organs," Alegre said. "You have to deal not only with the response against the graft, but also the response against the bacteria that come with the graft."

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