Cross-reactive memory CD8(+) T cells alter the immune response to heterologous secondary dengue virus infections in mice in a sequence-specific manner
Graduate School of Biomedical Sciences; Center for Infectious Disease and Vaccine Research
Medical Subject Headings
Animals; CD8-Positive T-Lymphocytes; Cross Reactions; Dengue Hemorrhagic Fever; Dengue Virus; Disease Models, Animal; Immunologic Memory; Interferon-gamma; Mice; Mice, Inbred BALB C; Serotyping; Tumor Necrosis Factor-alpha
Life Sciences | Medicine and Health Sciences
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.
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Citation: J Infect Dis. 2008 Feb 15;197(4):608-17. Link to article on publisher's site