Nov. 25, 2003 Scientists at the Emory Vaccine Center and The Scripps Research Institute have found a way to identify which of the T cells generated after a viral infection can persist and confer protective immunity. Because these long-lived cells protect against reinfection by "remembering" the prior pathogen, they are called memory T cells. This discovery about the specific mechanisms of long-term immunity could help scientists develop more effective vaccines against challenging infections.
The research, by Susan M. Kaech, PhD, a postdoctoral fellow in microbiology and immunology at Emory University School of Medicine, and principal investigator Rafi Ahmed, PhD, director of the Emory Vaccine Center and a Georgia Research Eminent Scholar, was published online November 16 and will be printed in the December issue of Nature Immunology. Other members of the research team were E. John Wherry and Bogumila T. Konieczny of Emory University School of Medicine, and Joyce T. Tan and Charles D. Surh of The Scripps Research Institute.
During an acute viral infection, CD4 and CD8 T cells activated by specific viral antigens dramatically expand in number and become effector T cells. These cells kill the virus-infected cells and also produce cytokines. Most effector cells die within a few weeks, after their initial job is complete. Only about 5 to 10 percent survive to become long-term memory cells, which are capable of mounting a strong and rapid immune response when they come into contact with the original virus, even years later. Scientists have not clearly understood the mechanisms of memory cell production, and a major unanswered question has been how to distinguish the small fraction of cells likely to survive in long-term memory.
This team of investigators found that expression of the interleukin 7 (IL-7) receptor, which binds the cytokine IL-7 and is required for T cell survival, is increased in a small subset of CD8 T cells generated during an acute infection, and that expression of this receptor marks those that will survive to become long-lived memory CD8 T cells.
In experiments with mice, the Emory scientists found that at the peak of the CD8 T cell immune response during an acute viral infection a small subset of effector cells had a higher expression of the IL-7 receptor, and they hypothesized that these cells would be the ones to survive as memory cells. They transferred a group of cells with and without this distinguishing characteristic into mice that were unexposed to virus, and found that in fact the cells expressing IL-7 receptor survived and differentiated into long-lived memory cells. They also found that IL-7 signals were necessary for the survival of these cells.
"We can consider the IL-7 receptor a marker of 'cellular fitness' for long-term survival and functionality," says Dr. Kaech. "This new knowledge should help us in assessing and predicting the number and quality of memory T cells that will be generated after infection or immunization. It also could lead to the identification of additional markers of memory cells and provide a more comprehensive picture of memory cell development."
"As scientists struggle to create long-term, effective vaccines for difficult diseases, they need a detailed understanding of the mechanisms of long-term memory," says Dr. Ahmed. "Understanding immune memory is the necessary basis for developing any type of effective vaccine. In addition, these findings could help in designing immunotherapies to control chronic viral infections and cancer."
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