CD8(+) T Cell-Mediated Immune Responses in West Nile Virus (Sarafend Strain) Encephalitis Are Independent of Gamma Interferon

J Gen Virol. 2006 Dec;87(Pt 12):3599-609. doi: 10.1099/vir.0.81306-0.

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.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Brain / pathology
  • Brain / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytotoxicity Tests, Immunologic
  • Disease Models, Animal
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology*
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Survival Analysis
  • West Nile Fever / immunology*
  • West Nile Fever / pathology
  • West Nile Fever / virology
  • West Nile virus / immunology*

Substances

  • Interferon-gamma