CD4+ T-cell effectors inhibit Epstein-Barr virus-induced B-cell proliferation.
In immunodeficient hosts, Epstein-Barr virus (EBV) often induces extensive B-cell lymphoproliferative disease and lymphoma. Without effective in vitro immune surveillance, B cells infected by the virus readily form immortalized cell lines. In the regression assay, memory T cells inhibit the formation of foci of EBV-transformed B cells that follows recent in vitro infection by EBV. No one has yet addressed which T cell regulates the early proliferative phase of B cells newly infected by EBV. Using new quantitative methods, we analyzed T-cell surveillance of EBV-mediated B-cell proliferation. We found that CD4+ T cells play a significant role in limiting proliferation of newly infected, activated CD23+ B cells. In the absence of T cells, EBV-infected CD23+ B cells divided rapidly during the first 3 weeks after infection. Removal of CD4+ but not CD8+ T cells also abrogated immune control. Purified CD4+ T cells eliminated outgrowth when added to EBV-infected B cells. Thus, unlike the killing of EBV-infected lymphoblastoid cell lines, in which CD8+ cytolytic T cells play an essential role, prevention of early-phase EBV-induced B-cell proliferation requires CD4+ effector T cells.
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
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Nikiforow
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Bottomly
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Miller
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size; D002478:Cells, Cultured; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D018655:Lymphocyte Count; D017455:Receptors, IgE / Q000378:metabolism; D012699:Serology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology
D019309:Epstein-Barr Virus Nuclear Antigens; D017455:Receptors, IgE; D016559:Tacrolimus