Mechanism of selective nonspecific cell-mediated cytotoxicity of virus-infected cells

Abstract

STUDIES of mechanisms of resistance to herpes simplex virus (HSV) in mice have demonstrated antibody-dependent cell-mediated cytotoxicity (AD-CMC) of HSV-infected cells exposed in suspension cultures to anti-HSV sera and normal mouse peritoneal cells (PC) or human peripheral blood leukocytes. In this system it was impossible to demonstrate T-cell-mediated cytotoxicity1–3. In an attempt to adjust the assay conditions to permit detection of such cytotoxicity by immune spleens or PC, the “monolayer” system of Gardner et al.4 was examined in syngeneic, allogeneic and xenogeneic combinations. Target cell monolayers were infected with HSV and exposed to immune or normal mouse PC. The latter produced unexpectedly high levels of nonspecific release of 51Cr by the monolayer HSV-infected cells. Because nonspecific or non-selective killing of human tumour cells5 by lymphocytes from normal patients has been a major problem in human tumour immunology, we have investigated the mechanism of this nonspecific cell-mediated cytotoxicity in the HSV system. Our results indicate that selective nonspecific killing is a consequence of the cross linking of effector and target cells through aggregated immunoglobulins.