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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3439-3447
Epstein-Barr Virus Induces Fas (CD95) in T Cells and Fas Ligand in B
Cells Leading to T-Cell Apoptosis
Jerome E. Tanner and
Caroline Alfieri
From the Department of Pediatrics, Children's Hospital of Eastern
Ontario, University of Ottawa Medical School, Ottawa, Ontario, Canada;
and the Laboratory of Molecular Virology, Ste-Justine Hospital Research
Center, Department of Microbiology and Immunology, University of
Montréal, Montréal, Québec, Canada.
Epstein-Barr virus (EBV) acute infectious mononucleosis (AIM) is
characterized by transient immunosuppression in vivo and increased
T-cell apoptosis after ex vivo culture of AIM peripheral blood
mononuclear cells. We undertook experiments to test whether EBV or
purified virion envelope glycoprotein gp350 could contribute to
Fas-mediated T-cell apoptosis. Our in vitro results indicate that EBV
increased Fas expression in CD4+ T cells and Fas ligand
(FasL) expression in B cells and macrophages. Purified gp350 was also
shown to significantly increase CD95 expression in CD4+ T
cells. When T-cell CD95 was cross-linked, EBV-stimulated T cells
underwent apoptosis. The induction of T-cell CD95 by EBV followed by
CD95 cross-linking with anti-CD95 monoclonal antibody resulted in a
loss in the number of T cells responding to the T-cell mitogens,
anti-CD3 antibody, and interleukin-2. These results indicate that, in
addition to serving as a principal ligand for the attachment of virus
to target cells, gp350 may also act as an immunomodulatory molecule
that promotes T-cell apoptosis.
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