Autoimmunity is the immune system’s Jekyll-and-Hyde transformation. Normally benevolent, protective cells–T cells–reveal a dark side by attacking the body’s healthy tissue. But new research suggests that in nerve injury, this usually destructive behavior of T cells may not be all bad.
In experiments on rats, Israeli and U.S. researchers find that T cells primed for autoimmune behavior may actually preserve nerves after a damaging blow.
“What has been thought of as a destructive, Mr. Hyde response may be more like Dr. Jekyll,” says investigator Michal Schwartz of the Weizmann Institute of Science in Rehovot, Israel. She and her colleagues report their findings in the June Journal of Neuroscience.
More than 11,000 people suffer spinal cord injuries each year in North America alone, says John D. Steeves of the Collaboration on Repair Discoveries, a spinal cord research group at the University of British Colombia in Vancouver. In most cases, the spinal cord is crushed but not completely severed, he notes. Researchers have sought ways to preserve the remaining nerve cells.
Preservation is a challenge because cell damage in the spinal cord doesn’t end with the initial trauma. Cells destroyed by an impact subsequently bleed toxic chemicals into their surroundings, killing neighboring nerve cells, Steeves explains. “There is a cascade of secondary cell damage, not dissimilar to when you bruise your knee,” says Steeves.
The arrival of T cells that have been sensitized to nerve tissue by an injury can cause inflammation, aggravating this process of secondary damage. T cells can also incite a full-blown autoimmune disease, in which the immune system chronically attacks healthy nerve cells.
However, Schwartz and her colleagues report four experiments showing that sensitized, or activated, T cells instead reduced the death of injured nerve cells in the animals.
In one experiment, the team from the Weizmann Institute, a company called Proneuron in Ness-Ziona, Israel, and Harvard Medical School in Boston compared the survival of cells in the optic nerves of two groups of rats. One group had been subjected to a spinal cord injury several days before receiving an optic-nerve injury. The other rats were subjected to only the second injury. Forty percent more nerve cells survived the optic injury in the first group of rats than in the second group. The researchers suspect that T cells activated in the previous injury protected cells damaged in the second insult.
In another experiment, the researchers removed the thymus gland, in which T cells mature, from one group of rats soon after birth. Those animals had 40 percent more cell death in injured optic nerves than rats with an intact thymus gland did.
In a third experiment, rats that received a dose of immune cells from other rats whose spinal cords were injured retained much greater walking capability after a subsequent injury than did animals that didn’t receive the treatment. Finally, the survival of optic nerve cells was higher in rats genetically engineered to overproduce certain T cells than it was in normal rats.
Steeves calls the results fascinating, but he points out that Schwartz didn’t determine whether the number of T cells rose at the animals’ injury sites. He also emphasizes that any therapy using activated T cells would have to prevent attacks on nerves long after an injury.
The team’s report shows “that in certain cases, activated immune cells can be part of the recovery process and actually prevent nerve cell injury,” says Esther M. Sternberg of the National Institute of Mental Health.
Adds Schwartz: “This shows for the first time that [in these cases] autoimmunity is not a mistake but a beneficial response.” However, the scientists still consider its mechanism to be a mystery.