"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 facto
Contact: Gwen Ericson
Washington University School of Medicine