Anti-dengue efforts ranging from awareness campaigns to fogging may be commonplace in tropical countries, but did you know that there is a vaccine against dengue? If you didn’t, there’s probably a simple reason why: it isn’t perfect.
Although effective on people who have contracted dengue before, the vaccine increases the risk of severe dengue and hospitalization in people who have never had the disease. This unfortunate reaction is most likely due to complications with immune system memory and multiple dengue serotypes.
Now, a team of researchers led by Laura Rivino at Duke-NUS Medical School and the University of Bristol, and Evan Newell at the A*STAR Singapore Immunology Network (SIgN) and Fred Hutchinson Cancer Research Center, are taking a computational immunology approach to studying T cells, which are central to the immune response against dengue infection.
Using mass cytometry and a peptide-human leukocyte antigen tetramer staining strategy, the researchers isolated T cells from dengue patients at different time points of the disease, and probed the T cells with 430 dengue and control candidate epitopes. They tracked a large number of activation, tracking and differentiation markers in the T cells, painting a comprehensive picture of the T cells’ response to dengue infection.
In their study, they found that dengue-specific T cells differentiated into two major cell fates: CD57+ CD127- cells, which resemble memory cells that are terminally differentiated, and CD127+ CD57- cells, which resemble memory cells capable of proliferating. These cells continue to exist at elevated frequencies in the body for up to a year after infection.
“I used a tool called Cytofkit, which we developed in-house to analyze the data,” said Jinmiao Chen, a Principal Investigator at SIgN and a co-author of the study. “This tool was specifically designed and developed for analyzing mass cytometry data. It is a one-stop toolbox that allowed us to visualize and interpret the analysis results effectively.”
Although their observational study could not confirm the function of these two classes of memory cells, the team hypothesizes, based on existing research, that the CD57+ CD127- cells can kill rapidly once activated because they express granzyme B, a serine protease commonly found in natural killer cells, while the CD127+ CD57- cells can persist for a long time as memory cells and proliferate to make more memory cells.
The researchers plan on performing functional studies on both groups of dengue-specific T cells to confirm their hypothesis. Beyond dengue, Chen hopes to use similar methods to study human gastric cancer, to reveal how cancer cells escape immune surveillance.
The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN).