title: Presentation of epstein-barr virus latency antigens to CD8(+), interferon-gamma-secreting, T lymphocytes.
abstract: 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 immunosuppressed patients. Here we looked for IFN-gamma-producing T lymphocytes in the blood of healthy donors with a rapid enzyme-linked immunospot (ELISPOT) assay, comparing as antigen presenting cells monocytes and dendritic cells (DC) infected with recombinant vaccinia virus (rVV). We found a strong CD8(+) ELISPOT response to one or more of the EBNA 3A, 3B and 3C antigens in the PBMC from 14 / 18 donors. The sensitivity of the overnight ELISPOT assay was increased using DC as antigen-presenting cells, including 3 / 3 individuals who lacked ELISPOT in PBMC. In addition, DC could markedly expand EBV-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 our data provide more evidence for the efficacy of DC in eliciting rapid responses to EBV latency antigens in circulating CD8(+) T cells.
authors.affiliation: Laboratory of Cellular Physiology and Immunology Rockefeller University, New York, NY 10021-6399, USA. subklem@rockvax.rockefeller.edu
authors.forename: M
authors.initials: M
authors.lastname: Subklewe
authors.forename: A
authors.initials: A
authors.lastname: Chahroudi
authors.forename: K
authors.initials: K
authors.lastname: Bickham
authors.forename: M
authors.initials: M
authors.lastname: Larsson
authors.forename: M G
authors.initials: MG
authors.lastname: Kurilla
authors.forename: N
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: R M
authors.initials: RM
authors.lastname: Steinman
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D011995:Recombination, Genetic; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D017735:Virus Latency / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D007371:Interferon-gamma