title: Qualitative differences in brain-infiltrating T cells are associated with a fatal outcome in mice infected with Japanese encephalitis virus.
abstract: Japanese encephalitis (JE) is the most important form of viral encephalitis in Asia. The critical factors determining mortality and severity of JE virus (JEV) infection remain unclear. We identified brain-infiltrating T cells associated with a fatal outcome of JEV infection in mice. Dying mice were defined as those that lost more than 25 % of their body weight by day 13 and died by day 21, while surviving mice were defined as those that lost less than 10 % by day 13, based on the result of the survival time course study. Two groups of five mice that demonstrated brain virus titers of >1 × 10(6) pfu/g were randomly selected from the dying and surviving groups and used in the analyses. Cytokine patterns in brains were first examined, revealing a higher ratio of Th1-related cytokine genes in dying mice. The expression levels of CD3, CD8, CD25, and CD69 increased in JEV-infected mice relative to mock-infected mice. However, expression levels of these cell-surface markers did not differ between the two groups. T-cell receptor (TCR) usage and complementary determining region 3 (CDR3) sequences were analyzed in the brain-infiltrating T cells. T cells expressing VA8-1, VA10-1, and VB2-1 increased in both groups. However, the dominant T-cell clones as defined by CDR3 amino acid sequence differed between the two groups. The results indicate that the outcome of JEV infection, death or survival, was determined by qualitative differences in infiltrating T-cell clones with unique CDR3 amino acid sequences.
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases, Tokyo, 162-8640, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Shirai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hayasaka
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Kitaura
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Takasaki
authors.forename: Kouichi
authors.initials: K
authors.lastname: Morita
authors.forename: Ryuji
authors.initials: R
authors.lastname: Suzuki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurane
mesh_terms: D000818:Animals; D001835:Body Weight; D001921:Brain / Q000276:immunology* / Q000821:virology; D022801:Complementarity Determining Regions / Q000235:genetics; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000276:immunology* / Q000401:mortality*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell