CD4-CELLS INHIBIT GROWTH OF EPSTEIN-BARR VIRUS-TRANSFORMED B-CELLS THROUGH CD95-CD95 LIGAND-MEDIATED APOPTOSIS( T)

Greater than 90% of the human population acquire Epstein-Barr virus (E BV) in infancy and retain a lifelong latent infection without any clin ical consequences. Nevertheless EBV has been identified as the causal agent of infectious mononucleosis, and is associated with several tumo urs including endemic Burkitt's lymphoma and B cell lymphomas in immun osupressed patients, B cells infected with EBV are transformed in vitr o and grow continuously as lymphoblastoid cell lines, The growth of EB V-transformed a cells in vivo is controlled by the immune system, Stud ies on immunity to EBV have mainly focused on MHC class I-restricted C D8(+) 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 l ytic cycle antigens, gives rise to a predominantly CD4(+) T cell respo nse. Furthermore, the growth of EBV-infected B cells can also be regul ated by these activated CD4(+) T cells through apoptosis mediated by C D95-CD95 ligand (CD95L), CD95-CD95L-mediated apoptosis is an important mechanism of normal B cell growth regulation, As EBV-transformed B ce lls remain susceptible to this mechanism, the control of EBV in vivo m ay be not only by virus-specific CD8(+) cytotoxic T cell immunity but also by normal mechanisms of immune regulation of B cell growth.