Cytomegalovirus (CMV)-specific lysis of CMV-infected target cells can be mediated by both NK-like and virus-specific cytotoxic T lymphocytes.

The host response to cytomegalovirus (CMV) involves both humoral and cell-mediated immunity. Because virus-specific cytotoxicity appears to be associated with recovery from CMV infection, we have investigated spontaneous (NK) and cytotoxic T cell (Tc) activity against CMV-infected target cells in normal donors and infants with active CMV infection. Fresh mononuclear cells from seropositive donors expressed low-level, non-MHC-restricted cytotoxic activity that preferentially lysed CMV-infected but not uninfected autologous and allogeneic fibroblasts. No cytotoxic activity was observed when mononuclear cells from seronegative donors were studied. Mononuclear cells from infants with active CMV infection and mononuclear cells from seropositive adults that were pre-incubated with cell-free CMV antigen in bulk culture for 6 days had enhanced cytotoxic activity against CMV-infected target cells sharing one or more class I MHC determinants with the effector cell populations. Selective enrichment or depletion experiments were performed to characterize the effector cell populations involved in the augmented cytotoxic response following in vitro induction with CMV antigen. Purified E-rosette-forming cells expressed increased cytotoxic activity against both virus-infected fibroblasts and the NK target cell, K562. Depletion experiments with monoclonal antibodies and complement indicated that the CMV-specific cytotoxic response involves both an E-rosette-positive, T8+, M1- T-cell subset that most likely represents CMV-specific Tc, and an NK population that can be induced to differentiate by in vitro stimulation with CMV antigen following quantitative NK-cell depletion with monoclonal antibody, B73.1.