Association of dengue virus-specific polyfunctional T-cell responses with clinical disease severity in acute dengue infection.

ABSTRACT: INTRODUCTION:Although the role of dengue virus (DENV)-specific T cells in the pathogenesis of acute dengue infection is emerging, the functionality of virus-specific T cells associated with milder clinical disease has not been well studied. We sought to investigate how the functionality of DENV-NS3 and DENV-NS5 protein-specific T cells differ in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). METHODS:Using intracellular cytokine assays, we assessed the production of interferon ? (IFN?), tumor necrosis factor-? (TNF-?), macrophage inflammatory protein-1? (MIP-1?), and CD107a expression in adult patients with acute DF (n?=?21) and DHF (n?=?22). RESULTS:Quadruple cytokine-producing, polyfunctional DENV-NS3- and DENV-NS5-specific T cells were more frequent in those with DF when compared to those with DHF. While DENV-NS3- and DENV-NS5-specific T cells in patients with DF expressed IFN??>?TNF-??>?MIP-??>?CD107a, T cells of those with DHF predominantly expressed CD107a?>?MIP-1??>?IFN??>?TNF-?. Overall production of IFN? or TNF-? by DENV-NS3- and DENV-NS5-specific T cells was significantly higher in patients with DF. The majority of NS3-specific T cells in patients with DF (78.6%) and DHF (68.9%) were single-cytokine producers; 76.6% of DENV-NS5-specific T cells in those with DF and 77.1% of those with DHF, produced only a single cytokine. However, no significant association was found with polyfunctional T-cell responses and the degree of viraemia. CONCLUSIONS:Our results suggest that the functional phenotype of DENV-specific T cells are likely to associate with clinical disease severity.

SUBMITTER: Wijeratne DT 

PROVIDER: S-EPMC6842812 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature