"The beauty of the tetramer technology is that it can be applied to study T cell responses to any pathogen, from influenza to HIV to malaria. And tetramers give you both a more accurate and a much more rapid picture of the immune response," Dr. Altman explains. In his Science article, Dr. Doherty says that tetramer staining is "set to be the gold standard for quantifying virus-specific CD8+ T cells."
The Emory researchers also tested the CD8+ T cell response using sensitive assays that measure the production of interferon-gamma, a cytokine (a small protein secreted from a cell) produced by virus-specific T cells that is important in controlling the infection. The interferon-gamma assay also demonstrated a strong, virus-specific response by CD8+ T cells.
Studies using the LDA technique have underestimated the virus-specific T cell response, explains Dr. Ahmed, partly because it requires culturing the cells for one to two weeks, and only T cells that are capable of dividing and surviving for that long are counted. Since activated T cells are prone to die when restimulated with viral antigens, many of the antigen-specific T cells either die or do not divide enough to be counted.
After the initial CD8+ T cell viral response, about 95 percent of the T cells die and the remainder persist to become memory cells poised to respond to future invasions by the same virus. The assays used in the Emory study were also able to detect memory CD8+ T cells specific to the LCMV virus more than one year after infection.
"One of the hardest things to do is to identify T cells responding to a particular pathogen," explains Dr. Ahmed. "This work greatly revises our thinking on the dynamics of T cell activation and will lead us to re-examine our models of viral-induced T cell proliferation."
This research was supported by grants from the National Institutes of
Health and the American Cancer Societ
Contact: Holly Korschun
Emory University Health Sciences Center