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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.

Original publication

DOI

10.1093/intimm/10.8.1149

Type

Journal article

Journal

Int Immunol

Publication Date

08/1998

Volume

10

Pages

1149 - 1157

Keywords

Acyclovir, Antibodies, Monoclonal, Antigens, Viral, Antiviral Agents, Apoptosis, B-Lymphocytes, CD4-Positive T-Lymphocytes, Cell Line, Cell Line, Transformed, Cell Transformation, Viral, Cytotoxicity, Immunologic, Fas Ligand Protein, Flow Cytometry, Herpesvirus 4, Human, Humans, Jurkat Cells, Lymphocyte Cooperation, Membrane Glycoproteins, Mitomycins, Tetradecanoylphorbol Acetate, fas Receptor