Researchers have identified a previously hidden link between our immune system and the activation of cells that lead to organ rejection.
The discovery opens the way for scientists to develop new forms of treatment that could prevent immune responses from attacking life-saving tissue transplants without leaving the body so open to infection or cancer.
A type of receptor on bone marrow cells called signal regulatory protein alpha (SIRPα) has been identified by scientists from the University of Pittsburgh as the body’s watchdog responsible for dispatching the lymphocytes that target and destroy foreign cells.
In simple terms, whenever we take cells from another person’s body and put them into our own, white blood cells see them as foreign and attempt to break them apart.
Not only is this bad news for the transplanted tissues, the swelling and fever that comes with the immune response isn’t exactly a picnic either.
The mechanisms behind the white blood cell assault are fairly well understood – molecules on the outside of the cells belonging to what’s called the major histocompatibility complex (MHC) identify them as different.
A type of white blood cell called a T lymphocyte has receptors on its surface capable of recognising unknown MHC proteins and responds by attempting to break up the foreign material they’re attached to.
Lymphocytes aren’t born knowing what’s foreign and what’s not; they need to be taught. Which is the job of another part of the immune system called a dendritic cell.
Dendritic cells chew up foreign proteins and weave them into their own MHC before displaying them on their surface like a microscopic ‘wanted’ poster. They then migrate into the body’s lymph nodes where they interact with the gun-slinging T lymphocytes.
Exactly how dendritic cells identify foreign materials, however, has been something of a mystery.
To learn more, the researchers studied the transplanted tissues in mice engineered to lack certain white blood cells such as their T lymphocytes.
They found that differences between the mice donor’s and recipient’s SIRPα gene correlated with the recipient’s immune responses.
SIRPα isn’t an unknown protein, already understood to bind to another protein called CD47 that triggers a range of immune responses in different white blood cells.
Joining the dots, the researchers believe CD47 on monocytes – the white blood cells that grow into dendritic cells – interact with SIRPα receptors on foreign tissues, setting off the entire ID check process.