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Cytokine production in response to Epstein‐Barr virus infection of peripheral blood mononuclear cells in vitro
Author(s) -
WHITTINGHAM SENGA,
NASELLI GAETANO,
HARRISON LEONARD C.,
BOYD ANDREW W.,
CEBON JONATHAN,
JACK IAN
Publication year - 1993
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.1993.30
Subject(s) - peripheral blood mononuclear cell , cytokine , immunology , tumor necrosis factor alpha , immune system , biology , virus , antigen , granulocyte macrophage colony stimulating factor , antibody , in vitro , interferon , virology , biochemistry
Summary To obtain a better understanding of the immune response to Epstein‐Barr virus (EBV), we measured the cytokines tumour necrosis factor (TNF)‐α/β, interleukin‐2 (IL‐2), interferon‐gamma (IFN‐γ), IL‐6 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in the conditioned medium of peripheral blood mononuclear cells from 10 healthy adults before and at 48 h and at 1, 2, 3 and 4 weeks following infection in vitro with EBV. Cultures were examined for regression of outgrowths of nascent virus‐transformed B cells, and populations of cells in the cultures were analysed by flow cytometry. TNF‐α/β was not detected in infected or non‐infected cultures. In infected cultures assayed at the nominated times, the highest levels of IL‐2 were detected at 48 hours, IFN‐γ at 1 week, IL‐6 at 2 weeks and GM‐CSF between 2 and 4 weeks. IL‐6 and GM‐CSF, but not IL‐2 or IFN‐γ, were detected in non‐infected cultures but at lower levels than in infected cultures. Nine of the 10 healthy adults showed regression of outgrowths of virus‐transformed B cells and, of these, seven had antibodies to the EBV capsid antigen (VCA). Strong regression was associated with sequential increases in IL‐2, IFN‐γ, and low levels of IL‐6 and GM‐CSF. Absent or weak regression was associated with an undetectable level of IL‐2, a low level of IFN‐γ, high levels of IL‐6 and GM‐CSF and an increased frequency of cells bearing the phenotype CD20 and HLA‐DR in the final weeks of culture. The percentage of cells with a phenotypic marker for natural killer cells remained constant in all cultures over the 4 week period, and there was a modest decrease in the percentage of T cells in both infected and non‐infected cultures. The demonstration of different temporal profiles of cytokines is in accord with a programmed cellular immune response to EBV infection which could serve as a model to study the events that modulate the inflammatory response to EBV.