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EBioMedicine. 2016 Nov;13:284-293. doi: 10.1016/j.ebiom.2016.10.006. Epub 2016 Oct 7.

Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection.

Author information

1
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.
2
Department of Veterinary Medicine, National Taiwan University, Taiwan.
3
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.
4
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States. Electronic address: sujan@lji.org.

Abstract

Infection with one of the four dengue virus serotypes (DENV1-4) presumably leads to lifelong immunity against the infecting serotype but not against heterotypic reinfection, resulting in a greater risk of developing Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) during secondary infection. Both antibodies and T cell responses have been implicated in DHF/DSS pathogenesis. According to the T cell-based hypothesis termed "original antigenic sin," secondary DENV infection is dominated by non-protective, cross-reactive T cells that elicit an aberrant immune response. The goal of our study was to compare the roles of serotype-specific and cross-reactive T cells in protection vs. pathogenesis during DENV infection in vivo. Specifically, we utilized IFN-α/βR-/- HLA*B0702 transgenic mice in the context of peptide vaccination with relevant human CD8 T cell epitopes. IFN-α/βR-/- HLA*B0702 transgenic mice were immunized with DENV serotype 2 (DENV2)-specific epitopes or variants found in any of the other three serotypes (DENV1, DENV3 or DENV4), followed by challenge with DENV. Although cross-reactive T cell responses were lower than responses elicited by serotype-specific T cells, immunization with either serotype-specific or variant peptide epitopes enhanced viral clearance, demonstrating that both serotype-specific and cross-reactive T cells can contribute to protection in vivo against DENV infection.

KEYWORDS:

Cross-reactivity; Dengue; T cells; Vaccination

PMID:
27746192
PMCID:
PMC5264312
DOI:
10.1016/j.ebiom.2016.10.006
[Indexed for MEDLINE]
Free PMC Article

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