Detecting an intruder, the body sounds an alarm, alerting fighter cells to the site. How this intricate feat is pulled off - with immune cells coursing through the body's circulatory system knowing exactly which "exit"to take into nearby affected tissues - has mystified scientists for years (see previous page). Now researchers at the Weizmann Institute of Science have discovered that equally important lessons may be gleaned from cells that perform the exact opposite - running away from trouble like the plague.
Dr. Idit Shachar of the Institute's Immunology Department and her Ph.D. student Liat Flaishon found that young B cells (a class of immune cells known as lymphocytes) veer away from distressed areas, in marked contrast to their adult counterparts. Shachar wondered what mechanism was protecting them from getting caught on the front lines at a young age, when they were ill-equipped to survive. And more importantly, she thought, could this mechanism possibly be used to remove adult immune cells from the battlefield when, as occasionally happens, the immune response goes awry, attacking the body itself?
Inappropriate immune responses occur when the body's call for help turns out to be a false alarm and, in the absence of an invader the mobilized lymphocytes end up attacking the host, or when lymphocytes overreact at the height of an attack. This kind of attack could cause problems ranging from mild inflammation to life-threatening diseases, including asthma, multiple sclerosis, and diabetes.
Shachar's team found that in contrast to adult lymphocytes, which have long been known to secrete high levels of a substance called interferon gamma, young B-cells secrete only minute levels of this substance. Small quantities of interferon gamma short-circuit the young B-cells' ability to reach the site of trouble.
After discerning this substance's exact mode of action, Shachar and her group, including Dr. Ian Topilski and Flaishon (who is also a physician), set out to determine whether interferon gamma could indeed be used to inhibit the combative action of adult immune cells. To do so, they created an asthma model using mice. Asthma, a very common inflammatory disease, is a particularly dangerous immunological overreaction, in which lymphocytes swarm the lymph nodes of the lungs, thickening the bronchial walls and making breathing difficult or impossible.
The results of the initial experiments were encouraging: Minute doses of interferon gamma dramatically reduced bronchial inflammation in asthmatic mice. Shachar now plans to administer interferon gamma to mice during late-stage asthmatic episodes to determine whether it can alleviate an acute crisis. Ultimately, she intends to apply the treatment to asthmatic humans - an experiment for which Ichilov Hospital has recently given approval. Concurrently, she is running experiments using interferon gamma to suppress other types of inflammation and has achieved heartening preliminary results for colitis.
Dr. Shachar's research is supported by the Harry and Jeanette Weinberg Fund for the Molecular Genetics of Cancer; the Philip M. Klutznick Fund, Chicago, IL; the Weizmann Institute of Science - Yale Exchange Program; Mr. Mauricio Gerson, Mexico; and Mr. Udi Angel, Israel. She is the incumbent of the Trudy and Alvin Levine Career Development Chair.