B cell, cross-priming, herpesvirus, T cell, dendritic cell, DNA primers
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.
Bickham, K., K. Goodman, C. Paludan, S. Nikiforow, M. L. Tsang, R. M. Steinman, and C. Münz. 2003. "Dendritic Cells Initiate Immune Control of Epstein-Barr Virus Transformation of B Lymphocytes in Vitro." Journal of Experimental Medicine 198 (11): 1653-1663