title: CD8+ T cells prevent antigen-induced antibody-dependent enhancement of dengue disease in mice.
abstract: 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.
authors.affiliation: Center for Infectious Disease, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: Raphaël M
authors.initials: RM
authors.lastname: Zellweger
authors.affiliation: Center for Infectious Disease, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: William E
authors.initials: WE
authors.lastname: Eddy
authors.affiliation: Center for Infectious Disease, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: William W
authors.initials: WW
authors.lastname: Tang
authors.affiliation: Center for Infectious Disease, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: Robyn
authors.initials: R
authors.lastname: Miller
authors.affiliation: Center for Infectious Disease, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037 sujan@lji.org.
authors.forename: Sujan
authors.initials: S
authors.lastname: Shresta
mesh_terms: D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D019067:Antibody-Dependent Enhancement / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D003716:Dengue Virus / Q000276:immunology*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D019562:Viral Load / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007074:Immunoglobulin G