Association of Intracellular Balance in CD4+ T-cells and MIP- in CD8+ T-cells with Disease Severity in Adults with Dengue

Background: We tested the hypothesis that dengue haemorrhagic fever (DHF) is associated with a $T_H1$-skewed immune response as opposed to dengue fever (DF). Methods: We estimated intracellular (in T-cells) and serum levels of designate $T_H1/T_H2$ cytokines [interferon-${\gamma}$ (IFN-${\gamma}$), interleukin-4 (IL-4), and tumor necrosis factor-${\alpha}$] and macrophage inflammatory protein-$1{\alpha}$ (MIP-$1{\alpha}$) at admission, 48h, and day 5 in 20 adults with dengue (DF=10, DHF=10) and 10 dengue-naive healthy controls. Results: At admission, intracellular IFN-${\gamma}$/IL-4 ratio in CD4+ T-cells and proportion of MIP-$1{\alpha}$-positive CD8+ T-cells were significantly higher in patients with DHF [7.21 (5.36~10.81) vs. 3.04 (1.75~4.02); p=0.011 and 6.2% (3.2~8.2%) vs. 2.4% (2.0~3.6%); p=0.023]. The latter showed a significant positive correlation with IFN-${\gamma}$/IL-4 ratio in CD4+ T-cells (Spearman's rho=0.64; p=0.003), percentage-change in haematocrit (rho=0.47; p=0.048), and serum alanine amino-transferase level (rho=0.61; p=0.009). Conclusion: We conclude that DHF is associated with a $T_H1$-skewed immune response. Further, MIP-$1{\alpha}$ in CD8+ T-cells is an important immunologic correlate of disease severity in dengue.