title: Altered effector functions of virus-specific and virus cross-reactive CD8+ T cells in mice immunized with related flaviviruses.
abstract: Memory cross-reactive CD8+ T-cell responses may induce protection or immunopathology upon secondary viral challenge. To elucidate the potential role of T cells in sequential flavivirus infection, we characterized cross-reactive CD4+ and CD8+ T-cell responses between attenuated and pathogenic Japanese encephalitis virus (JEV) and pathogenic West Nile virus (WNV). A previously reported WNV NS4b CD8+ T-cell epitope and its JEV variant elicited CD8+ T-cell responses in both JEV- and WNV-infected mice. The peptide variant homologous to the immunizing virus induced greater cytokine secretion and activated higher frequencies of epitope-specific CD8+ T cells. However, there was a virus-dependent, peptide variant-independent pattern of cytokine secretion; the IFNgamma+-to-IFNgamma+TNFalpha+ CD8+ T-cell ratio was greater in JEV- than in WNV-infected mice. Despite similarities in viral burden for pathogenic WNV and JEV viruses, CD8+ T cells from pathogenic JEV-immunized mice exhibited functional and phenotypic profiles similar to those seen for the attenuated JEV strain. Patterns of killer cell lectin-like receptor G1 (KLRG1) and CD127 expression differed by virus type, with a rapid expansion and contraction of short-lived effector cells in JEV infection and persistence of high levels of short-lived effector cells in WNV infection. Such cross-reactive T-cell responses to primary infection may affect the outcomes of sequential flavivirus infections.
authors.affiliation: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Derek W
authors.initials: DW
authors.lastname: Trobaugh
authors.forename: Liyan
authors.initials: L
authors.lastname: Yang
authors.forename: Francis A
authors.initials: FA
authors.lastname: Ennis
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003429:Cross Reactions; D004664:Encephalitis Virus, Japanese / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D018177:Flavivirus Infections / Q000276:immunology* / Q000821:virology; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014613:Vaccines, Attenuated; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology; D014779:Virus Replication; D014902:West Nile virus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D008222:Lymphokines; D009842:Oligopeptides; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D007371:Interferon-gamma