Dengue is the most prevalent arthropod-borne viral disease worldwide and is caused by the four dengue virus serotypes (DENV-1-4). Sequential heterologous DENV infections can be associated with severe disease manifestations. Here, we present an immunocompetent mouse model of secondary DENV infection using non mouse-adapted DENV strains to investigate the pathogenesis of severe dengue disease. C57BL/6 mice infected sequentially with DENV-1 (strain Puerto Rico/94) and DENV-2 (strain Tonga/74) developed low platelet counts, internal hemorrhages, and increase of liver enzymes. Cross-reactive CD8+ T lymphocytes were found to be necessary and sufficient for signs of severe disease by adoptively transferring of DENV-1-immune CD8+T lymphocytes before DENV-2 challenge. Disease signs were associated with production of tumor necrosis factor (TNF)-α and elevated cytotoxicity displayed by heterotypic anti-DENV-1 CD8+ T lymphocytes. These findings highlight the critical role of heterotypic anti-DENV CD8+ T lymphocytes in manifestations of severe dengue disease.
Pubmed ID: 28483582 RIS Download
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View all literature mentionsThis monoclonal targets CD8α
View all literature mentionsCell line Vero is a Spontaneously immortalized cell line with a species of origin Chlorocebus sabaeus
View all literature mentionsMus musculus with name B6;129S-Tnftm1Gkl/J from IMSR.
View all literature mentionsMus musculus with name B6.129S2-Cd8atm1Mak/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line Vero is a Spontaneously immortalized cell line with a species of origin Chlorocebus sabaeus
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis monoclonal targets CD8α
View all literature mentionsMus musculus with name B6;129S-Tnftm1Gkl/J from IMSR.
View all literature mentionsMus musculus with name B6.129S2-Cd8atm1Mak/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line Vero is a Spontaneously immortalized cell line with a species of origin Chlorocebus sabaeus
View all literature mentionsThis monoclonal targets CD8α
View all literature mentionsMus musculus with name B6;129S-Tnftm1Gkl/J from IMSR.
View all literature mentionsMus musculus with name B6.129S2-Cd8atm1Mak/J from IMSR.
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