Presentation of Epstein-Barr virus latency antigens to CD8(+), interferon-gamma-secreting, T lymphocytes

Epstein-Barr virus (EBV) infects more than 95% of the human population and causes an asymptomatic life-long infection in the majority of EBV carriers. Cell-mediated immunity provides resistance to EBV, as demonstrated by the occurrence of EBV-induced post-transplant lymphoproliferative disease in im munosuppressed patients. Here we looked for IFN-gamma-producing T lymphocyt es in the blood of healthy donors with a rapid enzyme-linked immunospot (EL ISPOT) assay, comparing as antigen presenting cells monocytes and dendritic cells (DC) infected with recombinant vaccinia virus (rVV). We found a stro ng CD8(+) ELISPOT response to one or more of the EBNA 3A, 3B and 3C antigen s in the PBMC from 14/18 donors. The sensitivity of the overnight ELISPOT a ssay was increased using DC as antigen-presenting cells, including 3/3 indi viduals who lacked ELISPOT in PBMC. In addition, DC could markedly expand E BV-specific spots after a 7-day culture. In a smaller number of donors, we documented recognition of the subdominant LMP 1, LMP 2 and EBNA 1 antigens that are expressed in a variety of EBV-associated malignancies. Therefore o ur data provide more evidence for the efficacy of DC in eliciting rapid res ponses to EBV latency antigens in circulating CD8(+) T cells.