T-cell suicide stops mice fighting off flu

日期:2019-03-01 05:19:01 作者:庞氯 阅读:

By Wendy Zukerman More bad press for free radicals. Now it seems that too many of them can impair the mouse immune system, making them unable to fight off flu. The finding could shed light on the cause of many mysterious human immunodeficiency disorders, such as severe combined immunodeficiency (SCID), says Frederick Domann at the University of Iowa, Iowa city. Free radicals are natural by-products of metabolism, which bind to molecules, including proteins and DNA. But oxidative damage is linked to many diseases such as lung cancer, atherosclerosis and Alzheimer’s. However, no one knew if free radicals also affected an important arm of the immune system which uses T-cells. A type of white blood cell, T-cells are supposed to attack invaders but they can also malfunction, leading to autoimmune disorders. Domann and colleagues created mice with elevated levels of a free radical called superoxide by knocking out the gene SOD2, which normally mops up superoxide. Elevated levels of superoxide had “severe effects on T-cell development,” says Domann. Normally, when T-cells are no longer working properly they self-destruct in a process called apoptosis. This is to prevent them attacking the body’s own cells. According to Domann, excess free radicals appear to alter the signalling process responsible for apoptosis, prompting functional T-cells to suicide unnecessarily. “Superoxide makes these cells die in very high numbers,” he says. Since a properly functioning SOD2 is fundamental to all mammals “we would expect a similar result in humans”, says Domann. Without a complete repertoire of T-cells the mice were unable to fight off flu. All died when their immune system faced H1N1 compared to only 20 per cent of healthy mice. Domann reasoned that too few free radicals might also lead to problems. “It’s the flip side,” he says. “Without enough oxidants, dysfunctional T-cells aren’t encouraged to self-destruct.” To test the theory, Domann gave healthy mice antioxidant drugs. It boosted their T-cell count, but did not improve their recovery from influenza when compared with untreated mice. Domann hypothesises that the extra T-cells probably aren’t functional and should normally have died. While in this short-term study the mice did not acquire autoimmune disorders, “free radicals have to remain on the table as a culprit” and tested in future studies, he says. Tony Tiganis a molecular biologist at Monash University, Australia says, “The assumption is that free radicals are detrimental, but that’s not true.” This study shows that both oxidants and antioxidants “have an important role” in the immune system, he says. Journal Reference: Free Radical Biology and Medicine, DOI: 10.1016/j.freeradbiomed.2010.11.025 More on these topics: