doi:10.1038/nindia.2016.133 Published online 13 October 2016
Millions get infected by dengue virus globally but a better understanding about the immunological responses in patients during clinical disease has been lacking. Now, in a joint study, researchers in India, Thailand and the USA report1 "the most comprehensive analysis" of immune blood cells in dengue patients that has important implications for developing better vaccines.
The CD8 T cells are a class of lymphocytes (blood cells) that are of particular interest from vaccination perspective because of their role in eliminating virus infected targets through cytotoxic effect. In the case of dengue, however, it has been thought that these cells, while giving protection, might also contribute to disease.
Though the CD8 T cells' association with dengue disease had been investigated earlier, many gaps remain. "Our studies for the first time provide a comprehensive description of the phenotypes, functions and molecular profiles of two major subsets of CD8 T cells," the authors say.
The researchers analysed CD8 T cells derived from peripheral blood of 153 confirmed dengue cases – 108 from New Delhi and 45 from Bangkok – "by using a combination of phenotypic, functional and transcriptomic approaches."
They found that, following dengue infection, the CD8 T cells "massively expand in numbers and show phenotypes that indicate migration to tissues and the ability to kill virus infected cells." In fact, the expansion of the CD8 T cells seen in dengue patients appear to be strikingly higher than that reported in other flavivirus infections such as yellow fever, or respiratory infections like influenza, says the report.
According to the study, results obtained in dengue patients from India and Thailand were alike. Further, the gene expression profiles of these cells appeared strikingly similar in dengue patients across continents, including South America indicating that properties of these CD8 T cells are similar in dengue patients from different geographical regions.
Most importantly the study showed that a vast majority of CD8 T cells do not produce "cytokine interferon gamma (IFN-γ)," that is involved in regulating the immune system's response to inflammation and infection. This was "rather surprising," the authors say, considering the proliferative expansion and activation of these cells and their strong cytotoxic effect.
"Since these cells do not produce the IFN-γ, they are likely to be protective than pathogenic during dengue," Shahid Jameel, a virologist and CEO of Wellcome Trust/DBT India Alliance told Nature India. The finding has "important implications for developing better dengue vaccines," he said.
The authors conclude that an understanding of the mechanism by which the CD8 T cells lose their capacity to produce IFN-γ can potentially open up novel therapeutics avenues to modulate inflammation and its pathological consequences in disease like dengue.
1. Chandele, A. et al. Characterization of CD8 T cells in dengue disease. J. Virol. (2016) doi: 10.1128/JVI.01424-16