title: Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus.
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 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.
authors.affiliation: Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taiwan.
authors.forename: Hsuen-Chin
authors.initials: HC
authors.lastname: Chen
authors.forename: Show-Yun
authors.initials: SY
authors.lastname: Lai
authors.forename: Jui-Min
authors.initials: JM
authors.lastname: Sung
authors.forename: Shu-Hwae
authors.initials: SH
authors.lastname: Lee
authors.forename: Yu-Chin
authors.initials: YC
authors.lastname: Lin
authors.forename: Wei-Kung
authors.initials: WK
authors.lastname: Wang
authors.forename: Yee-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Chuan-Liang
authors.initials: CL
authors.lastname: Kao
authors.forename: Chwan-Chuen
authors.initials: CC
authors.lastname: King
authors.forename: Betty A
authors.initials: BA
authors.lastname: Wu-Hsieh
mesh_terms: 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
chemical_list: 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