Epstein-Barr virus induces Fas (CD95) in T cells and Fas ligand in B cellsleading to T-cell apoptosis

Epstein-Barr virus (EBV) acute infectious mononucleosis (AIM) is characteri zed by transient immunosuppression in vive and increased T-cell apoptosis a fter ex vive culture of AIM peripheral blood mononuclear cells. We undertoo k experiments to test whether EBV or purified virion envelope glycoprotein gp350 could contribute to Pas-mediated T-cell apoptosis. Our in vitro resul ts indicate that EBV increased Fas expression in CD4(+) T cells and Fas lig and (FasL) expression in B cells and macrophages. Purified gp350 was also s hown to significantly increase CD95 expression in CD4(+) T cells. When T-ce ll CD95 was cross-linked, EBV-stimulated T cells underwent apoptosis. The i nduction of T-cell CD95 by EBV followed by CD95 cross-linking with anti-CD9 5 monoclonal antibody resulted in a loss in the number of T cells respondin g to the T-cell mitogens, anti-CD3 antibody, and interleukin-2. These resul ts indicate that, in addition to serving as a principal ligand for the atta chment of virus to target cells, gp350 may also act as an immunomodulatory molecule that promotes T-cell apoptosis. (C) 1999 by The American Society o f Hematology.