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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 γ 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. herpesvirus regression assay cross-priming T cell B cell Footnotes The online version of this article includes supplemental material. Abbreviations used in this paper: CSA, cyclosporin A; EBV, Epstein-Barr virus; HD, Hodgkin's disease; IM, infectious mononucleosis; LCL, lymphoblastoid cell line; PTLD, posttransplant lymphoproliferative disease; vv, vaccinia viruses. Submitted: 21 April 2003 Accepted: 10 October 2003
The Journal of Experimental Medicine – Rockefeller University Press
Published: Dec 1, 2003
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