Dendritic cells initiate immune control of epstein-barr virus transformation of B lymphocytes in vitro.
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.
Bickham
Kara
K
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
Goodman
Kiera
K
Paludan
Casper
C
Nikiforow
Sarah
S
Tsang
Ming Li
ML
Steinman
Ralph M
RM
Münz
Christian
C
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
D017931:DNA Primers