Such drugs do not interfere with essential protective immune function since bacterial proteins that normally trigger immune defense do so when they enter lymph nodes -- "where the T cells are essentially trapped by the drug for a few days, but still are working fine and allowing new antibody formation," he explains.
Treatment using this drug strategy does not come without risks, Goetzl cautions. Current drugs that affect one type of S1P receptor affect all others as well, and some of these control heart rate and muscle development. In clinical trials of some of these kinds of drugs, a number of patients have tired easily, experienced lower blood flow and a tendency for airways to constrict as muscle walls develop abnormally, Goetzl says.
"Fully exploiting this approach for treatment of autoimmune diseases and transplant rejection will depend on developing new drugs that block only the immune type of S1P receptor," he adds. "But early studies by a number of researchers are quite promising."
Progress will also come from finding "uniquely effective combinations of these agents with other immunosuppressive drugs," he says.
In animal studies and clinical research with patients over more than a decade, scientists have come to understand that millions of T cells and B cells are "called" into lymph nodes by other immune molecules called chemokines.
"But we began to wonder why T cells don't always swarm into lymph nodes and flood on into blood vessels that lead to all parts of the body," Goetzl says. "We asked ourselves, 'What is the brake?'"
In research with mice that have T cells that lack S1P receptors or have over-expressed receptors, the Goetzl and Rosen labs and others determined that T cells have on their surfaces what are known as G pr
Source:University of California - San Francisco