title: Dendritic cells initiate immune control of epstein-barr virus transformation of B lymphocytes in vitro.
abstract: The initiation of cell-mediated immunity to Epstein-Barr virus (EBV) has been analyzed with cells from EBV-seronegative blood donors in culture. The addition of dendritic cells (DCs) is essential to prime naive T cells that recognize EBV-latent antigens in enzyme-linked immunospot assays for interferon gamma secretion and eradicate transformed B cells in regression assays. In contrast, DCs are not required to control the outgrowth of EBV-transformed B lymphocytes from seropositive donors. Enriched CD4+ and CD8+ T cells mediate regression of EBV-transformed cells in seronegative and seropositive donors, but the kinetics of T-dependent regression occurs with much greater speed with seropositives. EBV infection of DCs cannot be detected by reverse transcription-polymerase chain reaction with primers specific for mRNA for the EBNA1 U and K exons. Instead, DCs capture B cell debris and generate T cells specific for EBV latency antigens. We suggest that the cross-presentation of EBV-latent antigens from infected B cells by DCs is required for the initiation of EBV-specific immune control in vivo and that future EBV vaccine strategies should target viral antigens to DCs.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Bickham
authors.forename: Kiera
authors.initials: K
authors.lastname: Goodman
authors.forename: Casper
authors.initials: C
authors.lastname: Paludan
authors.forename: Sarah
authors.initials: S
authors.lastname: Nikiforow
authors.forename: Ming Li
authors.initials: ML
authors.lastname: Tsang
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002472:Cell Transformation, Viral / Q000276:immunology*; D018920:Coculture Techniques; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D010587:Phagocytosis
chemical_list: D017931:DNA Primers