Interferon-gamma protects human endothelial cells from lymphokine-activated killer cell-mediated lysis

In adoptive immunotherapy the lymphokine-activated killer (LAK) cells, known to be cytotoxic to many tumor cell lines, are injected i.v. into tumor-bearing animals or cancer patients. However, in addition to a significant reduction in tumor masses, complications occur in many cases, most severe of which are the vascular leak syndrome and hypotension. In this report we show that LAK cells are also cytotoxic to normal vascular endothelial cells, which may partly contribute to these complications. Incubation of the endothelial cells with interferon-gamma (IFN-gamma), but not with interleukin 1 (IL 1) or tumor necrosis factor, protects the endothelial cells from LAK-mediated lysis in a dose- and time-dependent manner. The protective effect is abolished by monoclonal antibody against IFN-gamma. However, the IFN-gamma treatment does not protect LAK-sensitive tumor cell lines from LAK-mediated lysis. Concomitantly IFN-gamma also induces both class I and class II antigens on endothelial cells. The induction of these major histocompatibility complex (MHC) antigens does not explain the protective effect: timewise, the protection is complete already within 24 h after addition of IFN-gamma to endothelial cell culture, whereas the induction of MHC antigens peaks at 72 h, and antibodies against these antigens are not able to abolish the protective effect.