Cytokine production in response to Epstein-Barr virus infection of peripheral blood mononuclear cells in vitro.
To obtain a better understanding of the immune response to Epstein-Barr virus (EBV), we measured the cytokines tumour necrosis factor (TNF)-alpha/beta, interleukin-2 (IL-2), interferon-gamma (IFN-gamma), 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-alpha/beta 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-gamma 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-gamma, 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-gamma, 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-gamma, 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Whittingham
S
S
Burnet Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Vic., Australia.
Naselli
G
G
Harrison
L C
LC
Boyd
A W
AW
Cebon
J
J
Jack
I
I
D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D002472:Cell Transformation, Viral / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D014412:Tumor Virus Infections / Q000276:immunology
D000914:Antibodies, Viral; D015703:Antigens, CD; D016207:Cytokines