Cross-reactive memory CD8(+) T cells alter the immune response to heterologous secondary dengue virus infections in mice in a sequence-specific manner

J Infect Dis. 2008 Feb 15;197(4):608-17. doi: 10.1086/526790.

Abstract

Dengue virus is the causative agent of dengue fever and the more-severe dengue hemorrhagic fever (DHF). Human studies suggest that the increased risk of DHF during secondary infection is due to immunopathology partially mediated by cross-reactive memory T cells from the primary infection. To model T cell responses to sequential infections, we immunized mice with different sequences of dengue virus serotypes and measured the frequency of peptide-specific T cells after infection. The acute response after heterologous secondary infections was enhanced compared with the acute or memory response after primary infection. Also, the hierarchy of epitope-specific responses was influenced by the specific sequence of infection. Adoptive-transfer experiments showed that memory T cells responded preferentially to the secondary infection. These findings demonstrate that cross-reactive T cells from a primary infection alter the immune response during a heterologous secondary infection.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / virology*
  • Cross Reactions
  • Dengue Virus / immunology*
  • Disease Models, Animal
  • Immunologic Memory
  • Interferon-gamma / immunology
  • Mice
  • Mice, Inbred BALB C
  • Serotyping
  • Severe Dengue / immunology*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Tumor Necrosis Factor-alpha
  • Interferon-gamma