CD4+ T cells inhibit growth of Epstein-Barr virus-transformed B cells through CD95-CD95 ligand-mediated apoptosis.
Greater than 90% of the human population acquire Epstein-Barr virus (EBV) in infancy and retain a lifelong latent infection without any clinical consequences. Nevertheless EBV has been identified as the causal agent of infectious mononucleosis, and is associated with several tumours including endemic Burkitt's lymphoma and B cell lymphomas in immunosupressed patients. B cells infected with EBV are transformed in vitro and grow continuously as lymphoblastoid cell lines. The growth of EBV-transformed B cells in vivo is controlled by the immune system. Studies on immunity to EBV have mainly focused on MHC class I-restricted CD8+ cytotoxic T cells specific for viral latent antigens. Here it is reported that in vitro stimulation of peripheral blood lymphocytes by autologous EBV-infected B cells, which have been induced to express lytic cycle antigens, gives rise to a predominantly CD4+ T cell response. Furthermore, the growth of EBV-infected B cells can also be regulated by these activated CD4+ T cells through apoptosis mediated by CD95-CD95 ligand (CD95L). CD95-CD95L-mediated apoptosis is an important mechanism of normal B cell growth regulation. As EBV-transformed B cells remain susceptible to this mechanism, the control of EBV in vivo may be not only by virus-specific CD8+ cytotoxic T cell immunity but also by normal mechanisms of immune regulation of B cell growth.
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, UK.
A D
AD
Wilson
I
I
Redchenko
N A
NA
Williams
A J
AJ
Morgan
D000212:Acyclovir / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000956:Antigens, Viral / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008211:Lymphocyte Cooperation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008937:Mitomycins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019014:fas Receptor / Q000032:analysis / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000998:Antiviral Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D008937:Mitomycins; D019014:fas Receptor; D013755:Tetradecanoylphorbol Acetate; D000212:Acyclovir