INTERLEUKIN-2 PROTECTS HAIRY LEUKEMIC-CELLS FROM LYMPHOKINE-ACTIVATEDKILLER CELL-MEDIATED CYTOTOXICITY

Interleukin 2 (IL-2) activates natural killer cells and generates lymp hokine-activated killer (LAK) cell-mediated cytotoxicity. In ''adoptiv e immunotherapy,'' a combination of LAK administration and IL-2 infusi on was found to be effective therapy for some tumors and ineffective f or others. Here we report a novel function for IL-2, its ability to pr otect tumor cells (cell lines obtained from hairy cell leukemia patien ts) against LAK activity. The protective effect induced by IL-2 is sim ilar to that induced by interferon (IFN). Protection by both cytokines requires new mRNA/protein synthesis; both IL-2 and IFN reduce the abi lity of tumor target cells to trigger LAK effector cells following bin ding between these two types of cells. However, endogenous IFN is not the mediator of the IL-2 protective effect against LAK activity since monoclonal antibodies against IFN-alpha and IFN-gamma did not abolish the protective effect of IL-2. In addition, IL-2 does not induce the e xpression of class I major histocompatibility complex antigens on the target cell surface, believed to be the signal for the IFN-induced pro tection against natural killer and LAK activities. Finally, leukemic c ells resistant to IFN-alpha did respond to IL-2 treatment and became l ess sensitive to LAK cytotoxicity. Thus the ability of IL-2 to protect tumor cells from LAK activity may explain the lack of response to ado ptive immunotherapy in tumors that express the IL-2 receptor.