Interferon-γ control of EBV-transformed B cells: A role for CD8⁺ T cells that poorly kill EBV-infected cells

Control of Epstein-Barr virus (EBV) infection requires CD8⁺ T cells. Surprisingly, many EBV-specific CD8⁺ T cells kill autologous EBV-transformed B lymphoblasts poorly. We investigated the effector functions used by poorly cytotoxic EBV-specific CD8⁺ D7 cloned T cells and by EBV-stimulated peripheral blood lymphocytes. D7 T cells did not inhibit B lymphoblast growth in long-term coculture, but prevented the outgrowth of newly infected autologous B cells. Optimally stimulated D7 T cells and EBV-stimulated peripheral blood lymphocytes produced interferon (IFN)-γ at levels that inhibited EBV-transformed B cell outgrowth. Inhibitory factor activity was neutralized by anti-IFN-γ monoclonal antibodies (mAb), but not by antibodies to several other cytokines. These data suggest an in vivo role for IFN-γ secreting EBV-specific CD8⁺ T cells.