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Immune mechanism could help explain transient immune suppression often seen in acute infections

Emory Health Sciences

Scientists have discovered that at the same time the immune system is vigorously attacking invading viruses or bacteria, it is unexpectedly reducing its production of a particular type of factor that directs the movement of immune cells. The new finding, which could help explain the transient immune suppression often seen during acute infections, shows that the immune system is even more complex than previously believed.

Results of the research by Emory scientists, along with colleagues at the University of California, San Francisco, will be published in the Aug. 3, 2007 issue of the journal Science. The research was conducted by Scott N. Mueller, PhD, postdoctoral fellow in the laboratory of Rafi Ahmed, PhD, director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar. The team also included Emory microbiologist Bogumila Konieczny and collaborators at the University of California, San Francisco and Cytos Biotechnology in Switzerland.

The research team, in a mouse study, focused on homeostatic chemokines--one of two major categories of molecular traffic cops in the immune system that directs the movement of immune cells. Also called lymphoid chemokines, these chemokines are responsible for guiding immune cells to the lymph nodes and spleen in healthy individuals and directing the cells to respond to antigens from invading viruses or bacteria.

Until now, scientists have believed these lymphoid chemokines were expressed in a steady state throughout life and that only a second type of chemokineÑknown as inflammatory chemokines--were expressed at varying levels in response to the threat of an invading pathogen. Inflammatory chemokines direct immune cells to go to particular sites, such as lung or skin, and fight off attackers during an active infection. The scientists discovered, however, that lymphoid chemokines do not remain in a steady state after all, but are reduced during the time of an active immune response.

The findings could help scientists devise better dosing schedules for multi-dose vaccines and also could provide a better understanding of how the immune system responds to multiple infections. A likely result is a lowering of the body's ability to respond to a second infection.

"If you have an acute viral infection, your immune system may be suppressed in its ability to respond to secondary infections during that brief period," Dr. Mueller says. "If you have a nasty flu infection in the lung, for example, you are more susceptible to secondary bacterial infections, and this chemokine reduction could contribute to that."

"The wonderful thing about immune cells is their ability to travel through the entire body, searching for pathogens and foreign antigens," said Dr. Mueller. "There has been considerable research performed on both groups of chemokines and their role in the immune response and immune trafficking. We know how important the lymphoid chemokines are in controlling the way cells move in the body. Until now, however, we believed these were expressed at a steady level in the immune tissues in healthy individuals.

"The discovery of this basic phenomenon--that these lymphoid chemokines are reduced during an immune response--was quite a shock to us. It illustrates another dramatic level of complexity in the immune system and demonstrates in greater detail how the traffic of immune cells is regulated."

Dr. Mueller believes the down-regulation of lymphoid chemokines, which occurs for a one- to two-week period during the height of an immune response, may be the body's way of shutting down the immune response and avoiding excessive and damaging inflammation. In addition, reducing these immune factor could be beneficial for the immune cells that are actively responding to a virus, he points out.

In a massive inflammatory response to infection, many immune cells divide into great numbers of cells, Dr. Mueller explains. Once the immune response is complete, 95 percent of those cells die and leave a smaller population of memory cells to circulate in the body and protect against subsequent infections by that same pathogen. Certain factors, or substrates, such as interleukins and cytokines, are important to nurture and keep these responding cells alive in the lymphoid tissues, but there is competition for the nurturing substrates between the cells that are actively responding to an infection and cells not responding. The down-regulation of lymphoid chemokines could be the body's way of keeping non-responding cells out of the competition, says Mueller.

Dr. Mueller also believes the discovery could have important implications for vaccine development, particularly those vaccines that require a prime/boost strategy, where giving a second dose too early, when chemokines are reduced, could make that dose less effective.

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