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

BackgroundIn 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.\n\nMethodology/Principal findingsUsing ex vivo IFN{gamma} 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, early appearance of DENV-specific T cell responses was significantly associated with milder clinical disease (p=0.02). DENV peptide specific T cell responses inversely correlated with the degree of viraemia, which was most significant for DENV-NS3 specific T cell responses (Spearmans 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, DENV-IgG inversely correlated with the degree of thrombocytopenia and levels of liver transaminases.\n\nConclusions/significanceEarly appearance of DENV-specific T cell IFN{gamma} responses appears to associate with milder clinical disease and resolution of viraemia, suggesting a protective role in acute dengue infection.