title: High clonality of virus-specific T lymphocytes defined by TCR usage in the brains of mice infected with West Nile virus.
abstract: It has been reported that brain-infiltrating T lymphocytes play critical roles in the clearance of West Nile virus (WNV) from the brains of mice. We characterized brain-infiltrating T lymphocytes by analyzing the TCR α- and β-chain repertoires, T cell clonality, and CDR3 sequences. CD3(+)CD8(+) T cells were localized in the WNV-infected brains. The expression of CD3, CD8, CD25, CD69, perforin, and granzymes positively correlated with viral RNA levels, and high levels of expression of IFN-γ, TNF-α, and IL-2 were detected in the brains, suggesting that Th1-like cytotoxic CD8(+) T cells are expanded in the brains in response to WNV infection. The brain-infiltrating T lymphocytes dominantly used TCR genes, VA1-1, VA2-1, VB5-2, and VB8-2, and exhibited a highly oligoclonal TCR repertoire. Interestingly, the brain-infiltrating T lymphocytes had different patterns of TCR repertoire usages among WNV-, Japanese encephalitis virus-, and tick-borne encephalitis virus-infected mice. Moreover, CD8(+) T cells isolated from the brains of WNV-infected mice produced IFN-γ and TNF-α after in vitro stimulation with peritoneal cells infected with WNV, but not with Japanese encephalitis virus. The results suggest that the infiltrating CD8(+) T cells were WNV-specific, but not cross-reactive among flaviviruses. T cells from the WNV-infected brains exhibited identical or similar CDR3 sequences in TCRα among tested mice, but somewhat diverse sequences in TCRβ. The results indicate that WNV-specific CD3(+)CD8(+) T cells expanding in the infected brains are highly oligoclonal, and they suggest that TCR α-chains play a dominant and critical role in Ag specificity of WNV-specific T cells.
authors: Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, Kanagawa 228-0815, Japan.
authors: Kazutaka
authors: K
authors: Kitaura
authors: Yoshiki
authors: Y
authors: Fujii
authors: Daisuke
authors: D
authors: Hayasaka
authors: Takaji
authors: T
authors: Matsutani
authors: Kenji
authors: K
authors: Shirai
authors: Noriyo
authors: N
authors: Nagata
authors: Chang-Kweng
authors: CK
authors: Lim
authors: Satsuki
authors: S
authors: Suzuki
authors: Tomohiko
authors: T
authors: Takasaki
authors: Ryuji
authors: R
authors: Suzuki
authors: Ichiro
authors: I
authors: Kurane
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D002999:Clone Cells; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004195:Disease Models, Animal; D005260:Female; D019672:Genes, T-Cell Receptor; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014901:West Nile Fever / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D004279:DNA, Viral; D011948:Receptors, Antigen, T-Cell