CD8+ T Cells Prevent Antigen-Induced Antibody-Dependent Enhancement of Dengue Disease in Mice

Dengue virus (DENV) causes pathologies ranging from the febrile illness dengue fever to the potentially lethal severe dengue disease. A major risk factor for developing severe dengue disease is the presence of subprotective DENV-reactive Abs from a previous infection (or from an immune mother), which can induce Ab-dependent enhancement of infection (ADE). However, infection in the presence of subprotective anti–DENV Abs does not always result in severe disease, suggesting that other factors influence disease severity. In this study we investigated how CD8 + T cell responses influence the outcome of Ab-mediated severe dengue disease. Mice were primed with aluminum hydroxide–adjuvanted UV-inactivated DENV prior to challenge with DENV. Priming failed to induce robust CD8 + T cell responses, and it induced nonneutralizing Ab responses that increased disease severity upon infection. Transfer of exogenous DENV-activated CD8 + T cells into primed mice prior to infection prevented Ab-dependent enhancement and dramatically reduced viral load. Our results suggest that in the presence of subprotective anti–DENV Abs, efficient CD8 + T cell responses reduce the risk of Ab-mediated severe dengue disease.