Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus

J Med Virol. 2004 Jul;73(3):419-31. doi: 10.1002/jmv.20108.


Activation and expansion of dengue virus-specific T cells and abnormal liver functions in dengue patients have been documented. However, it remains to be determined whether T cells are involved in the pathogenic mechanism of dengue virus infection. In this study, immunocompetent C57BL/6 mice were employed to study dengue virus-induced T cell activation. Mice were inoculated with 10(8) PFU dengue virus serotype 2 strain 16681 by the intravenous route. Dengue viral core RNA was detected by RT-PCR in mouse serum, liver, spleen, and brain at different time points after infection. Splenic T cells were activated as evidenced by their expression of CD69 and O-glycosylated CD43 at as early as day 3 after infection. Splenic T cell expression of O-glycosylated CD43 and IFN-gamma production coordinately peaked at day 5. Coincided with the peak of splenic T cell activation was hepatic lymphocyte infiltration and elevation of liver enzymes. Flow cytometric analysis revealed the infiltrating CD8(+) T cell to CD4(+) T cell ratio was 5/3. After a second inoculation of dengue virus, hepatic T cell infiltration and liver enzyme levels increased sharply. The infiltrating hepatic CD8(+) T cell to CD4(+) T cell ratio increased to 5.8/1. A strong correlation was found between T cell activation and hepatic cellular infiltration in immunocompetent mice infected with dengue virus. The kinetics of liver enzyme elevation also correlated with that of T cell activation. These data suggest a relationship between T cell infiltration and elevation of liver enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antigens, CD / analysis
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Aspartate Aminotransferases / blood
  • Brain / virology
  • CD4-CD8 Ratio
  • Dengue / immunology*
  • Dengue / pathology*
  • Dengue Virus / pathogenicity*
  • Immunocompetence
  • Interferon-gamma / analysis
  • Lectins, C-Type
  • Leukosialin
  • Liver / enzymology
  • Liver / immunology
  • Liver / pathology*
  • Liver / virology
  • Liver Function Tests
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Viral / blood
  • Sialoglycoproteins / analysis
  • Spleen / virology
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Lectins, C-Type
  • Leukosialin
  • RNA, Viral
  • Sialoglycoproteins
  • Spn protein, mouse
  • Interferon-gamma
  • Aspartate Aminotransferases
  • Alanine Transaminase