Emory Report

February 21, 2000

 Volume 52, No. 22

Scientists discover immune response 'memory'

By Poul Olson

Immune memory cells do not require continuing stimulation from viral antigen to maintain their disease-fighting capabilities, according to research by Emory immunologists.

Instead, memory CD8 T-cells evolve their own independent "lifestyle" that allows them to retain a "response-ready" mode over the long term. This kind of detailed knowledge about how immune memory persists is crucial for the rational design of vaccines, according to Rafi Ahmed, director of the Emory Vaccine Research Center.

Results of the study, conducted by Ahmed and immunologists Kaja Murali-Krishna and John Altman, were published in a recent issue of the journal Science.

Individuals who acquire immunity to diseases such as measles, yellow fever, polio or rubella, either through exposure or through vaccination, are often capable of retaining that immunity for many years or even a lifetime.

Acute viral infections induce two types of long-term memory: humoral immunity, in which B-cells produce antibodies to prevent infection by viruses; and cellular immunity, in which T-cells activated by specific viral antigens kill the virus-infected cells and also produce cytokines--proteins that prevent the growth of viruses and make cells resistant to viral infection.

CD8 T-cells can be divided into three distinct populations: naïve, effector and memory cells. Naïve CD8 T-cells are activated and become effector cells in the presence of viral antigen. Major histocompatibility complex class I (MHC Class I) molecules play a primary role in this effector response by "presenting" antigen of inva-ding pathogens to T-cell receptors, which in turn recognize the pathogens and attack them.

This response lasts for only a few weeks, after which about 95 percent of effector cells die and the remainder become memory cells, poised to mount an even stronger and more rapid immune response to future invasions by the same virus.

"There has been considerable interest in determining whether the survival and response capabilities of memory T-cells are dependent upon continuing presentation of specific or cross-reactive antigens by MHC molecules," Ahmed said.

He and his colleagues used mice deficient in MHC Class I molecules to help answer the question. They exposed the mice to a certain viral infection that is normally resolved within two weeks, after which the mice establish long-term T-cell memory.

They found that, although naïve T-cells require ongoing contact with MHC Class I molecules to maintain themselves, memory T-cells can survive and also undergo slow division, without the MHC/T-cell interactions, until they reach homeostasis--their optimal limit of effectiveness. Not only do the memory T-cells persist indefinitely, they also retain their ability for rapid response, through cytokines, to repeat encounters with the original viral antigen.

"Understanding immunological memory is the necessary basis of developing any effective vaccine," Ahmed said. "No matter what type of vaccine you are working on, or for which disease, you need to understand the mechanisms of immune memory."

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