Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus
Journal
Journal of Medical Virology
Journal Volume
73
Journal Issue
3
Pages
419-431
Date Issued
2004
Author(s)
Chen H.-C.
Lai S.-Y.
Sung J.-M.
Lee S.-H.
Lin Y.-C.
Wang W.-K.
King C.-C.
Wu-Hsieh B.A.
Abstract
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 108 PFU dengue virus serotype 2 strain 16681 bythe 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-γ 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. ? 2004 Wiley-Liss, Inc.
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; CD4 antigen; CD69 antigen; CD8 antigen; DNA fragment; gamma interferon; Hermes antigen; leukosialin; liver enzyme; malate dehydrogenase; virus antibody; virus RNA; animal cell; animal model; animal tissue; article; cell infiltration; controlled study; cytokine production; Dengue virus; enzyme linked immunosorbent assay; flow cytometry; immunocompetence; immunohistochemistry; liver; liver injury; lymphocyte activation; mouse; nick end labeling; nonhuman; phenotype; reverse transcription polymerase chain reaction; spleen lymphocyte; T lymphocyte; Alanine Transaminase; Animals; Antigens, CD; Antigens, CD43; Antigens, Differentiation, T-Lymphocyte; Aspartate Aminotransferases; Brain; CD4-CD8 Ratio; Dengue; Dengue Virus; Immunocompetence; Interferon Type II; Liver; Liver Function Tests; Lymphocyte Activation; Mice; Mice, Inbred C57BL; RNA, Viral; Sialoglycoproteins; Spleen; T-Lymphocytes; Dengue virus
Type
journal article