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Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection
- Source :
- EBioMedicine, EBioMedicine, Vol 13, Iss C, Pp 284-293 (2016)
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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.<br />Highlights • Serotype-cross-reactive CD8 T cells elicit a polyfunctional immune response similar to the response elicited by serotype-specific CD8 T cells. • Serotype cross-reactive CD8 T cells play a role in protection against DENV infection in a HLA-B*0702 Transgenic IFN-α/βR−/− mouse model. There are four major subtypes (serotypes) of the mosquito-borne Dengue virus. Infection with a first serotype is generally asymptomatic, but secondary infection with a different serotype is capable of causing severe disease. T cells previously exposed to a first serotype and which produce an immune response to a second serotype are said to be cross-reactive. Using a mouse model engineered with human T cell features, we characterized the cross-reactive T cell response to live dengue virus serotypes and viral protein fragments. Our results suggested cross-reactive T cells contribute to control of and protection against infection by a second dengue serotype, rather than leading to more severe disease.
- Subjects :
- 0301 basic medicine
Male
DENV, dengue virus
lcsh:Medicine
Dengue virus
CD8-Positive T-Lymphocytes
medicine.disease_cause
Ab, antibody
Epitope
Dengue fever
Dengue
Mice
0302 clinical medicine
Cytotoxic T cell
Original antigenic sin
PBMC, Peripheral Blood Mononuclear Cells
lcsh:R5-920
ADE, antibody dependent enhancement
Vaccination
virus diseases
General Medicine
3. Good health
medicine.anatomical_structure
Phenotype
NS, non-structural
Cytokines
Female
lcsh:Medicine (General)
Research Paper
DHF, dengue hemorrhagic fever
Secondary infection
T cell
T cells
Mice, Transgenic
DSS, dengue shock syndrome
Biology
Cross Reactions
Serogroup
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
medicine
Animals
Antibody-dependent enhancement
IFN, interferon
Immunodominant Epitopes
HLA, human leukocyte antigen
lcsh:R
Cross-reactivity
biochemical phenomena, metabolism, and nutrition
Dengue Virus
medicine.disease
Virology
Disease Models, Animal
030104 developmental biology
HLA-B Antigens
Immunology
030215 immunology
ICS, intracellular cytokine staining
Subjects
Details
- ISSN :
- 23523964
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....054d2924e546be81d816103b7c19b957
- Full Text :
- https://doi.org/10.1016/j.ebiom.2016.10.006