Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus.
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.
Chen
Hsuen-Chin
HC
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taiwan.
Lai
Show-Yun
SY
Sung
Jui-Min
JM
Lee
Shu-Hwae
SH
Lin
Yu-Chin
YC
Wang
Wei-Kung
WK
Chen
Yee-Chun
YC
Kao
Chuan-Liang
CL
King
Chwan-Chuen
CC
Wu-Hsieh
Betty A
BA
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001219:Aspartate Aminotransferases / Q000097:blood; D001921:Brain / Q000821:virology; D016516:CD4-CD8 Ratio; D003715:Dengue / Q000276:immunology* / Q000473:pathology*; D003716:Dengue Virus / Q000472:pathogenicity*; D007121:Immunocompetence; D007371:Interferon-gamma / Q000032:analysis; D037181:Lectins, C-Type; D051917:Leukosialin; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008111:Liver Function Tests; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012367:RNA, Viral / Q000097:blood; D012795:Sialoglycoproteins / Q000032:analysis; D013154:Spleen / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D000410:Alanine Transaminase; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001219:Aspartate Aminotransferases; D007371:Interferon-gamma; D037181:Lectins, C-Type; D051917:Leukosialin; D012367:RNA, Viral; D012795:Sialoglycoproteins; D000099192:CD69 Antigens; C497863:Spn protein, mouse