Abstract
Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population.
Highlights
Dengue is the most prevalent arthropod-born viral disease in tropical and subtropical areas of the globe, affecting approximately 400 million people annually [1]
The immune response against the dengue virus is still under investigation and it is important to understand why the disease can be fatal in a small proportion of cases
We explored how an important cell type of the immune system, namely the CD8+ T cell, reacts during dengue infection
Summary
Dengue is the most prevalent arthropod-born viral disease in tropical and subtropical areas of the globe, affecting approximately 400 million people annually [1]. Dengue cases in Central and Latin America have increased almost five-fold in the last 30 years. During 2008, up to one million cases were reported in Americas, and higher numbers of deaths were documented in the South [2]. Brazil has been hard hit by the disease, accounting for more than 60% of the total reported cases in the Americas [2]. The continuing occurrence of the disease in resource limited countries and the lack of novel therapeutic approaches or a highly effective vaccine make dengue fever a neglected disease. Surveillance for dengue is absent in most countries, and no existing model for predicting an outbreak in endemic regions is widely available. It is important to increase our knowledge of disease pathogenesis, with the goal of developing new strategies to fight the epidemic
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