Regulatory T cells secreting IL-10 dominate the immune response to EBV latent membrane protein 1.
Viruses exploit a number of strategies to evade immune recognition. In this study, we describe a novel mechanism by which EBV, rather than avoiding detection, subverts the immune response by stimulating regulatory T cells that secrete IL-10. Human PBMC from all EBV-seropositive, but not -seronegative, donors responded to both purified latent membrane protein 1 and the corresponding immunodominant peptides with high levels of IL-10 secretion by CD4(+) T cells. These IL-10 responses, characteristic of T regulatory 1 cells, inhibited T cell proliferation and IFN-gamma secretion induced by both mitogen and recall Ag. It was confirmed that the inhibition was IL-10 dependent by the use of neutralizing Ab. The deviation of the immune response toward suppression is likely to be important in maintaining latency and EBV-associated tumors.
Marshall
Neil A
NA
Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.
Vickers
Mark A
MA
Barker
Robert N
RN
D017951:Antigen Presentation / Q000276:immunology; D024201:Bystander Effect / Q000276:immunology; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002455:Cell Division / Q000276:immunology; D002461:Cell Line, Transformed; D015536:Down-Regulation / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*
D017252:CD3 Complex; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D014763:Viral Matrix Proteins; D016753:Interleukin-10; D007371:Interferon-gamma