title: CD8(+) T cell-mediated immune responses in West Nile virus (Sarafend strain) encephalitis are independent of gamma interferon.
abstract: The flavivirus West Nile virus (WNV) can cause fatal encephalitis in humans and mice. It has recently been demonstrated, in an experimental model using WNV strain Sarafend and C57BL/6 mice, that both virus- and immune-mediated pathology is involved in WNV encephalitis, with CD8(+) T cells being the dominant subpopulation of lymphocyte infiltrates in the brain. Here, the role of activated WNV-immune CD8(+) T cells in mouse WNV encephalitis was investigated further. Passive transfer of WNV-immune CD8(+) T cells reduced mortality significantly and prolonged survival times of mice infected with WNV. Early infiltration of WNV-immune CD8(+) T cells into infected brains is shown, suggesting a beneficial contribution of these lymphocytes to recovery from encephalitis. This antiviral function was not markedly mediated by gamma interferon (IFN-gamma), as a deficiency in IFN-gamma did not affect mortality to two strains of WNV (Sarafend and Kunjin) or brain virus titres significantly. The cytolytic potential, as well as precursor frequency, of WNV-immune CD8(+) T cells were not altered by the absence of IFN-gamma. This was reflected in transfer experiments of WNV-immune CD8(+) T cells from IFN-gamma(-/-) mice into WNV-infected wild-type mice, which showed that IFN-gamma-deficient T cells were as effective as those from WNV-immune wild-type mice in ameliorating disease outcome. It is speculated here that one of the pleiotropic functions of IFN-gamma is mimicked by WNV-Sarafend-mediated upregulation of cell-surface expression of major histocompatibility complex antigens, which may explain the lack of phenotype of IFN-gamma(-/-) mice in response to WNV.
authors.affiliation: Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University (ANU), PO Box 334, Canberra, ACT 2601, Australia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University (ANU), PO Box 334, Canberra, ACT 2601, Australia.
authors.forename: Mario
authors.initials: M
authors.lastname: Lobigs
authors.affiliation: Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University (ANU), PO Box 334, Canberra, ACT 2601, Australia.
authors.forename: Eva
authors.initials: E
authors.lastname: Lee
authors.affiliation: Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University (ANU), PO Box 334, Canberra, ACT 2601, Australia.
authors.forename: Aulikki
authors.initials: A
authors.lastname: Koskinen
authors.affiliation: Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University (ANU), PO Box 334, Canberra, ACT 2601, Australia.
authors.forename: Arno
authors.initials: A
authors.lastname: Müllbacher
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016019:Survival Analysis; D014901:West Nile Fever / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014902:West Nile virus / Q000276:immunology*
chemical_list: D007371:Interferon-gamma