It may sound like a case of blame the victim, but researchers at Washington University School of Medicine in St. Louis have shown that cells in the central nervous system can sometimes send out signals that invite hostile immune system attacks.
In mice the researchers studied, this invitation resulted in damage to the protective covering of nerves, causing a disease resembling multiple sclerosis.
"It's been clear for quite a while that our own lymphocytes (white blood cells) have the ability to enter the central nervous system and react with the cells there," says John Russell, Ph.D., professor of molecular biology and pharmacology. "Under normal circumstances, the brain and the immune system cooperate to keep out those cells that might harm the brain. But in people with multiple sclerosis, they get in."
The researchers found that they could prevent destructive immune cells from entering nervous system tissue by eliminating a molecular switch that sends "come here" messages to immune cells. Ordinarily, flipping that switch would cause immune cells to rush to the vicinity of the cells that sent the signals and destroy whatever they consider a danger -- including nerve cell coatings.
But in the mice in which the switch was removed, the researchers saw that immune cells previously primed by the scientists to attack the central nervous system (CNS) did not enter the CNS, and the mice stayed healthy.
In contrast, normal mice treated with the same hostile immune cells had numerous immune cells in their CNS tissue and developed symptoms similar to multiple sclerosis.
"What allows the primed lymphocytes into the CNS are signals from the CNS asking them in," Russell says. "We determined that the astrocytes, the specialized cells that provide nutrients to neurons, are among the cells most active in sending signals to attract lymphocytes."
The molecular switch that sends the call to immune cells is termed the tumor necrosis factor receptor (TNFR). When TNFR is activated, it causes cells to send out signal molecules called chemokines that direct immune cells to the site of damage or infection. The researchers found that astrocytes in mice were producing chemokines in response to activation of their TNFR molecules.