Accumulation of T-cells with selected T-cell receptors in the brains of Japanese encephalitis virus-infected mice.
Japanese encephalitis is a severe central nervous system (CNS) disease with a high case fatality rate in humans. We characterized T-cells infiltrating the brain after infection with Japanese encephalitis virus (JEV) in a mouse model and determined the clonality of the infiltrating T-cells by analyzing the sequences of complementary determining region 3 (CDR3) of the T-cell receptor. C3H/He mice died after intraperitoneal infection with the JaTH160 strain of JEV, demonstrating CNS degeneration and prominent T-cell infiltration. The percentages of T-cells bearing the VA5-1, VA17-1, VA19-1, VB2-1, VB8-3 and VB13-1 subfamilies were significantly increased following infiltration of the brains in infected mice. Additionally, CDR3 size spectratyping revealed the oligoclonality in T-cells bearing VA11-1 and VA18-1. CDR3 amino acid sequences were then determined for the VA5-1, VA11-1, VA18-1, VB8-3 and VB13-1 subfamilies. There were high levels of identity and similarity in amino acid sequences of CDR3 in these T-cells. Quantitative real-time PCR analysis also revealed that CD8, interferon-gamma and tumor necrosis factor-alpha were highly expressed in the infected mouse brain. These results indicate that T-cells with high clonality and similarity infiltrate the JEV-infected mouse brain, and that these T-cells are mainly CD8-positive and have the Th1/Tc1 phenotype.
Fujii
Yoshiki
Y
Department of Virology 1, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Kitaura
Kazutaka
K
Nakamichi
Kazuo
K
Takasaki
Tomohiko
T
Suzuki
Ryuji
R
Kurane
Ichiro
I
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000737:chemistry; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004664:Encephalitis Virus, Japanese / Q000276:immunology; D004672:Encephalitis, Japanese / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D022801:Complementarity Determining Regions; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma