Around 150,000 organ transplants are performed worldwide each year, giving new hope to people suffering from chronic illness. In many cases, transplants work, saving the life of the person who receives the organ. But in other cases, the body treats the organ as foreign, mounts an immune attack, and rejects it.
In new research published in Immunology and Cell Biology, Dr Bin Li, Professor Weisan Chen* and colleagues have discovered that a particular cell plays an important role in the initiation of organ rejection.
“Matching an organ with a recipient involves a compatibility test,” explains Professor Chen. “A common blood type is needed, for example. So too is shared Human Leukocyte Antigen (HLA) typing. These are proteins on the surface of our cells, and they are critical to organ transplantation.”
“In successful transplants, the donor’s HLAs are recognised and accepted by the recipient’s immune system, often with the help of immune suppressive drugs. When it is not accepted or tolerated, miss-matched donor HLA can cause an immune response that can trigger organ rejection.”
How donor HLA contributes to organ rejection is not yet fully understood. The research team believe that particular dendritic cell subsets may hold the key.
“Dendritic cells act as the inspectors of the body,” says Chen. “They sample the environment for foreign contaminants, especially HLA proteins, and alert immune cells, called T cells, to act accordingly. If there is a contaminant HLA protein, the T cells mount an immune attack.”
“When dendritic cells encounter a donor organ, they immediately recognise that the environment is different. They capture the donor HLAs, send a signal that this organ is a foreign contaminant, and instruct the T cells to mount an immune attack against the perceived threat. This can result in organ rejection.”
The research team tested a range of dendritic cells. They have identified specific sub-sets that initiate or trigger this unwanted immune response.
Chen believes that it might be possible to reduce transplant rejection by manipulating these dendritic cells to send different signals to the T cells. “They could, for example, be programmed to display immune check-point molecules, which would promote immunotolerance, and turn off the organ-rejecting T cells,” he says.
“In the future it may be possible to manipulate these dendritic cell subsets to ensure that organs are tolerated by the recipient in the absence of immune suppressive drugs, increasing the likelihood of a successful transplant.”
*Dr Bin Li is a scientist from The Affiliated Hospital of Sun Yat-sen University, China, who visited La Trobe University in 2015-2016 on a scholarship from the China Scholarship Council. Weisan Chen is a professor at the La Trobe Institute for Molecular Science.