Contraction of T cell response not linked to clearance of infection.(Brief Article)

2002 JUL 3 - (NewsRx.com & NewsRx.net) -- The results of a new University of Iowa (UI) study challenge an old assumption about how the immune system responds to an infection and could have important implications for improving vaccine efficiency. The study appeared online in Nature Immunology in June 2002.

The ability of the immune system to remember infections it has already defeated, and to respond rapidly and effectively to them during future exposures, is the basis of vaccination strategies. This immune memory is the result of a complex set of molecular events that John Harty, PhD, UI associate professor of microbiology, and his colleagues are investigating.

Prior to infection or vaccination, the immune system contains a diverse reservoir of immature T cells. This large population of cells is composed of thousands of subgroups, each able to recognize different pathogens such as bacteria and viruses. When the system encounters a specific infection, the group of T cells that recognize that particular infection is rapidly mobilized. Over the space of several days, this population of cells expands from a few thousand to millions of cells, which then mature, developing the capability to fight off the infection. Finally, around 90% of the cells die off, leaving the remaining 10% as memory cells that maintain life-long protection against reinfection.

"This contraction of the T cell response is important as it sets the memory level. It also prevents T cells specific for only a single infection from taking over the immune system and hindering responses to new infection," Harty said. "Immunology textbooks teach that contraction occurs when the infection is cleared, suggesting that the immune system 'senses' this change and responds accordingly. In contrast, our work demonstrates that contraction of the T cell response is not linked to clearance of infection."

The UI researchers examined the timing and rate of T cell contraction during infections in mice. Various strategies were used to alter the duration of infection. In one experiment, mice infected with bacteria were given antibiotics to artificially shorten the duration of the infection. To study the alternative situation where an infection persists, the researchers used genetically modified mice that are unable to clear a viral infection. In both cases, the "die-off" stage of T cells followed the same pattern and timing. These experiments showed that T cell contraction is independent of whether an infection is still present. The results were similar for both bacterial and viral infections.

Harty explained that the finding that the contraction is "preprogrammed" could have implications for improving vaccine design.

"The immune response that we are studying is a very long and complicated process, and the cells go through many phases," Harty said. "But it looks like those phases are all controlled from ...