Cross-reactive memory CD8(+) T cells alter the immune response to heterologous secondary dengue virus infections in mice in a sequence-specific manner.
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.
Beaumier
Coreen M
CM
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Mathew
Anuja
A
Bashyam
Hema S
HS
Rothman
Alan L
AL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D003429:Cross Reactions; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012703:Serotyping; D019595:Severe Dengue / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma