Immune Netw.  2010 Oct;10(5):164-172. 10.4110/in.2010.10.5.164.

Association of Intracellular T(H)1-T(H)2 Balance in CD4+ T-cells and MIP-1alpha in CD8+ T-cells with Disease Severity in Adults with Dengue

• Kadhiravan T
• Saxena A
• Singh A
• Broor S
• Sharma SK
• Mitra DK

• KMID: 1456220
• DOI: http://doi.org/10.4110/in.2010.10.5.164

Abstract

BACKGROUND
We tested the hypothesis that dengue haemorrhagic fever (DHF) is associated with a T(H)1-skewed immune response as opposed to dengue fever (DF).
METHODS
We estimated intracellular (in T-cells) and serum levels of designate T(H)1/T(H)2 cytokines [interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and tumor necrosis factor-alpha] and macrophage inflammatory protein-1alpha (MIP-1alpha) at admission, 48 h, 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-1alpha-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 aminotransferase level (rho=0.61; p=0.009).
CONCLUSION
We conclude that DHF is associated with a T(H)1-skewed immune response. Further, MIP-1alpha in CD8+ T-cells is an important immunologic correlate of disease severity in dengue.

Keyword

Dengue haemorrhagic fever; Disease severity; Interferon-gamma; Interleukin-4; Macrophage inflammatory protein-1alpha

MeSH Terms

Adult
Alanine Transaminase
Chemokine CCL3
Cytokines
Dengue
Fever
Humans
Interferon-gamma
Interleukin-4
Macrophages
Necrosis
T-Lymphocytes
Alanine Transaminase
Chemokine CCL3
Cytokines
Interferon-gamma
Interleukin-4

Figure

• 

  Figure 1 Representative Flowcytometry Plots: Flow cytometry plots showing CD8 positive cytokine and chemokine producing T cells in DHF/DSS (Dengue hemorrhagic fever/Dengue shock syndrome), DF (Dengue fever) along with DN-H (Dengue negative healthy) individuals peripheral blood. X-axis of the graph shows CD8+ T cells and Y axis has cytokine and chemokines as measured in vitro on polyclonal stimulation.

• 

  Figure 2 A group-wise plot of the ratio of interferon-γ-(IFN-γ) positive to interleukin-4-(IL-4) positive CD4+ T-cells (A) and CD8+ T-cells (B) in dengue-naïve healthy controls (controls), patients with dengue fever (DF), and dengue haemorrhagic fever (DHF); horizontal lines across the data points depict the group median; a non-parametric test (Cuzick test) was applied to test for a linear trend across the three groups.

• 

  Figure 3 Scatter plots of percentage of MIP-1α-positive CD8+ T-cells against IFN-γ/IL-4 ratio in CD4+ T-cells (A), percentage-change in haematocrit (B), and serum alanine aminotransferase level (C); Gray lines represent the linear regression lines.

• 

  Figure 4 A plot of the IFN-γ/IL-4 ratio at baseline in CD4+ T-cells against the duration of fever at enrollment. Closed triangles (▴) depict dengue fever and the closed squares (▪) depict dengue haemorrhagic fever.

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