Woe to all who oppose the immune system! It's a formidable force, and when it goes haywire its minions wreak havoc on the body. Now, researchers have developed a way to help the immune system purge itself of troops run amok, halting the damage.
When foreign troublemakers, such as viruses, invade the body, immune cells called T cells are responsible for fighting them off. Like a police officer giving a bloodhound a fugitive's scent, immune cells called antigen-presenting cells hold up parts of foreign proteins, or antigens, to spur T cells into action. A protein embedded in the cell membrane of the T cell, called the T cell receptor, detects the antigen and tells the T cell to respond to the threat. Sometimes, though, T cells mobilize against the body's own proteins, causing autoimmune diseases such as diabetes or multiple sclerosis.
Selectively eliminating those T cells that recognize "self" antigens could alleviate autoimmune diseases, and pathologist Terrence Geiger of St. Jude Children's Research Hospital in Memphis, Tennessee, and colleagues turned some T cells into assassins to do the job. By rigging cells to perform the functions of both antigen-presenting cells and T cells, the researchers created a booby trap for the disease-causing T cells.
In mice with a disorder similar to multiple sclerosis, the immune system attacks a protein in nerve cells called myelin, leading to paralysis. The team fused the antigen that sparks the self-attack--myelin basic protein--to the part of the T cell receptor that transmits the "attack" message to the cell. They genetically engineered mice to produce T cells that carry the fused protein in their outer membranes. When mice with the autoimmune disorder were given the modified T cells from the engineered mice, the disease-causing T cells bound to the myelin antigen. That alerted the T cell receptor tacked onto the antigen and sprang the trap, signaling the modified T cell to kill the errant T cells. The modified cells both prevented the onset of the disease and, when given to sick mice, reversed the disease, the team reports online 11 November in Nature Biotechnology.
"It's certainly an exciting new observation," says immunologist Michel Sadelain of Memorial Sloan-Kettering Cancer Center in New York City. Although a number of obstacles remain before the approach can be applied to human disease, Sadelain says, genetically altered T cells "are emerging as very interesting therapeutic tools" for a variety of diseases.