Altered effector functions of virus-specific and virus cross-reactive CD8+ T cells in mice immunized with related flaviviruses

Eur J Immunol. 2010 May;40(5):1315-27. doi: 10.1002/eji.200839108.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Viral / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cross Reactions
  • Encephalitis Virus, Japanese / immunology*
  • Encephalitis Virus, Japanese / pathogenicity
  • Encephalitis Virus, Japanese / physiology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Flavivirus Infections / immunology*
  • Flavivirus Infections / virology
  • Immunization
  • Immunodominant Epitopes / immunology
  • Interferon-gamma / metabolism
  • Lymphokines / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Oligopeptides / immunology
  • Specific Pathogen-Free Organisms
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Vaccines, Attenuated
  • Viral Load
  • Viral Vaccines / immunology
  • Virus Replication
  • West Nile virus / immunology*
  • West Nile virus / pathogenicity
  • West Nile virus / physiology

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Lymphokines
  • Oligopeptides
  • Vaccines, Attenuated
  • Viral Vaccines
  • Interferon-gamma