Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection
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....
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| Format: | Article |
| Language: | English |
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Elsevier
2016-11-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416304613 |
| _version_ | 1830511357770858496 |
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| author | Annie Elong Ngono Hui-Wen Chen William W Tang Yunichel Joo Kevin King Daniela Weiskopf John Sidney Alessandro Sette Sujan Shresta |
| author_facet | Annie Elong Ngono Hui-Wen Chen William W Tang Yunichel Joo Kevin King Daniela Weiskopf John Sidney Alessandro Sette Sujan Shresta |
| author_sort | Annie Elong Ngono |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T02:09:27Z |
| format | Article |
| id | doaj.art-dd0fb073543a4e8b862a2aab1daa2921 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-22T02:09:27Z |
| publishDate | 2016-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-dd0fb073543a4e8b862a2aab1daa29212022-12-21T18:42:26ZengElsevierEBioMedicine2352-39642016-11-0113C28429310.1016/j.ebiom.2016.10.006Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus InfectionAnnie Elong Ngono0Hui-Wen Chen1William W Tang2Yunichel Joo3Kevin King4Daniela Weiskopf5John Sidney6Alessandro Sette7Sujan Shresta8Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United StatesDepartment of Veterinary Medicine, National Taiwan University, TaiwanDivision of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United StatesDivision of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United StatesDivision of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United StatesDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United StatesDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United StatesDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United StatesDivision of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United StatesInfection 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.http://www.sciencedirect.com/science/article/pii/S2352396416304613DengueCross-reactivityT cellsVaccination |
| spellingShingle | Annie Elong Ngono Hui-Wen Chen William W Tang Yunichel Joo Kevin King Daniela Weiskopf John Sidney Alessandro Sette Sujan Shresta Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection EBioMedicine Dengue Cross-reactivity T cells Vaccination |
| title | Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection |
| title_full | Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection |
| title_fullStr | Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection |
| title_full_unstemmed | Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection |
| title_short | Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection |
| title_sort | protective role of cross reactive cd8 t cells against dengue virus infection |
| topic | Dengue Cross-reactivity T cells Vaccination |
| url | http://www.sciencedirect.com/science/article/pii/S2352396416304613 |
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