IFN-γ Production and Cytotoxicity of IL-2-Activated Murine NK Cells Are Differentially Regulated by MHC Class I Molecules

Abstract

Abstract Activation of NK cells by target cells leads to cytotoxicity as well as production of various cytokines including IFN-γ. MHC class I molecules on target cells regulate NK cytotoxicity. However, little is known about the regulation of IFN-γ production by NK cells. We examined the production of IFN-γ in individual murine NK cells stimulated with tumor cell lines by flow cytometric analysis of intracellular IFN-γ. Among several tumor lines tested, the rat basophilic leukemia line RBL-1 induced particularly high level of IFN-γ production in IL-2-activated NK cells, whereas other lines, including the prototypic NK target YAC-1, induced very low or no IFN-γ production. Transfection of murine classical MHC class I molecules into RBL-1 cells substantially inhibited IFN-γ production. This inhibition of IFN-γ production by MHC class I was independent of Ly-49 or CD94/NKG2A expression on NK cells. These results indicate that some target cells directly stimulate IL-2-activated NK cells and induce IFN-γ production, but the requirements for the induction of IFN-γ production seem different from those for NK cytotoxicity. Furthermore, similar to NK cytotoxicity, induction of IFN-γ production is inhibited by MHC class I on stimulating cells. However, the MHC class I-specific receptors inhibiting IFN-γ production are different from those for NK cytotoxicity.