The regulation of protective immunity to viruses by L-selectin

点击翻译按钮获取中文摘要

Virus infections in animals and humans cause morbid and fatal diseases which incur a severe economic burden. The ability of animals and humans to combat viruses depends on a subset of white blood cells called T lymphocytes. When a virus enters the body, T lymphocytes are presented with virus extracts in local lymph glands and turned into killer T cells before they are despatched to fight the virus. Some killer T cells turn into memory T cells which remember the virus and prevent re-infection. How killer T cells find their way to virus infected tissues, such as influenza infected lungs, is not understood.Our latest work has identified a homing molecule on killer T cells, called L-selectin, that directs them to virus-infected tissues and maintains immune memory to that virus. L-selectin is lost from the surface of T lymphocytes as they turn into killer T cells. So more of it needs to be made by the killer T-cells before they leave the lymph glands, otherwise they can't sense detect infected cells in the body. By increasing the expression of L-selectin on killer T cells we can increase the number of killer T cells at the site of infection and boost killing of virus. However, if T lymphocytes do not make more L-selectin they are unable to locate where virus is growing and clear it from the bodyIn this proposal we want to find out how the level of L-selectin on the surface of killer T cells is controlled and what effect L-selectin has on memory T cells. We will also identify how L-selectin senses a virus-infected tissue by finding what binds to it to make T-lymphocytes go to the virus infected organs. There are currently no anti-viral drugs for many of the viruses that cause significant morbidity in animals and mortality in young and elderly humans. Furthermore, vaccines are either not available or need to be re-formulated every season, like with influenza. Our studies of killer T cell homing have revealed a new way of boosting the immune system. This is by increasing the homing of killer T cells to virus infected tissues. Understanding how L-selectin is involved in killer T cells will help to develop new approaches to combat viral infections in people and livestock.