The interleukin-10 homolog encoded by Epstein-Barr virus enhances the reactivation of virus-specific cytotoxic T cell and HLA-unrestricted killer cell responses.
We determined what influence the Epstein-Barr virus (EBV)-encoded homologue of IL-10 (viral or vIL-10) had on immune responses important for the control of EBV infection. We produced recombinant vIL-10 in a B cell line. A 17-kDa recombinant protein was secreted and had the same molecular weight as vIL-10 secreted by EBV-infected B cells. Functional activity of recombinant vIL-10 was shown by the inhibition of interferon-gamma production by activated leukocytes. Cytotoxic T cells and HLA-unrestricted activated killer cells are both important arms of the immune response to EBV. vIL-10, either expressed by B cell stimulators or added exogenously, enhanced the in vitro reactivation of allo- and EBV-specific cytotoxic T cells. vIL-10 also enhanced the activation of HLA-unrestricted killer cells by EBV-transformed B cells. In contrast, the interleukin-2-mediated activation of these killers was unaffected. Since vIL-10 is expressed during the lytic cycle of EBV, we conclude that the expression of vIL-10 may enhance immune responses to EBV-infected cells during periods of virus replication in vivo. In this way, the virus may limit its own replication and maintain the apathogenic virus carrier state that is characteristic of EBV.
Stewart
J P
JP
Department of Virology and Molecular Biology, St Jude Children's Research Hospital, Memphis, Tennessee 38101-0318.
Rooney
C M
CM
D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D006680:HLA Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins; D016753:Interleukin-10