Using novel assays described as the new "gold standard" for measuring specific immune responses to viruses, Emory University School of Medicine researchers have found that the response of CD8+ T cells, which provide the front line of protection against invading viruses, is considerably larger and much more targeted to specific viral antigens than scientists previously believed.
Although it is well known that T cells multiply in the body in response to viral infection, it has been difficult to measure the number of cells and exactly what they are responding to. The most common assay used to measure the response, the limiting dilution analysis (LDA) has led scientists to believe that only a small fragment (1 percent to 5 percent) of activated CD8+ T cells are responding to specific viral antigens, and that most of the T-cell response is a general, non-specific one.
Rafi Ahmed, Ph.D., Georgia Research Alliance Eminent Scholar in the Emory Department of Microbiology and Immunology and director of the Emory Vaccine Center; Kaja Murali-Krishna, Ph.D., a postdoctoral dellow in Dr. Ahmed's laboratory; and John Altman, Ph.D., Emory assistant professor of microbiology and immunology, used three novel assays to test the CD8+ T cell response to lymphocytic choriomeningitis virus (LCMV) in mice. They found that more than 70 percent of the activated CD8+ T cells were responding to specific antigens of LCMV -- a number they termed "remarkably high," and one that was 20 to 100 times greater than numbers based on LDA testing.
Based on these results, the Emory investigators calculated that virus-specific CD8+ T cells can rapidly expand >30,000 fold (about 15 divisions) in one week with an estimated doubling time of six to eight hours during the peak phase of the response.
The research was reported in the February issue of Immunity. Nobel
laureate Peter C. Doherty, in a commentary in the April 10 issue of Science,
Contact: Holly Korschun
Emory University Health Sciences Center