Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection

PLoS Negl Trop Dis. 2018 Oct 1;12(10):e0006540. doi: 10.1371/journal.pntd.0006540. eCollection 2018 Oct.


Background: In order to understand the role of dengue virus (DENV) specific T cell responses that associate with protection, we studied their frequency and phenotype in relation to clinical disease severity and resolution of viraemia in a large cohort of patients with varying severity of acute dengue infection.

Methodology/principal findings: Using ex vivo IFNγ ELISpot assays we determined the frequency of dengue viral peptide (DENV)-NS3, NS1 and NS5 responsive T cells in 74 adult patients with acute dengue infection and examined the association of responsive T cell frequency with the extent of viraemia and clinical disease severity. We found that total DENV-specific and DENV-NS3-specific T cell responses, were higher in patients with dengue fever (DF), when compared to those with dengue haemorrhagic fever (DHF). In addition, those with DF had significantly higher (p = 0.02) DENV-specific T cell responses on day 4 of infection compared to those who subsequently developed DHF. DENV peptide specific T cell responses inversely correlated with the degree of viraemia, which was most significant for DENV-NS3 specific T cell responses (Spearman's r = -0.47, p = 0.0003). The frequency of T cell responses to NS1, NS5 and pooled DENV peptides, correlated with the degree of thrombocytopenia but had no association with levels of liver transaminases. In contrast, total DENV-IgG inversely correlated with the degree of thrombocytopenia and levels of liver transaminases.

Conclusions/significance: Early appearance of DENV-specific T cell IFNγ responses before the onset of plasma leakage, appears to associate with milder clinical disease and resolution of viraemia, suggesting a protective role in acute dengue infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dengue / immunology
  • Dengue / pathology*
  • Dengue / virology
  • Dengue Virus / isolation & purification*
  • Enzyme-Linked Immunospot Assay
  • Female
  • Humans
  • Immunity, Cellular*
  • Interferon-gamma / analysis
  • Male
  • Severity of Illness Index
  • T-Lymphocytes / immunology*
  • Viral Load*
  • Viral Nonstructural Proteins / immunology


  • Viral Nonstructural Proteins
  • Interferon-gamma