INTERLEUKIN-10 REDUCES NATURAL-KILLER SENSITIVITY AND DOWN-REGULATES MHC CLASS-I EXPRESSION ON H-RAS-TRANSFORMED CELLS

We examined the effect of IL-10 on sensitivity to NK-cell-mediated cyt otoxicity of the H-ras-induced transformants, W14 and W31. Incubation of cells with recombinant human (rh) IL-10 resulted in a dose-dependen t decrease in the expression of MHC class I antigens, but not in the I CAM-1 expression. However, prior incubation of W31 cells with rhIL-10 markedly decreased their susceptibility to cytolysis by rat splenic NK cells. This fact suggested that the IL-10-mediated decrease in MHC cl ass I expression might not dominate the regulation of the NK sensitivi ty. This was true when rat IL-10 cDNA-introduced W31 cells were used a s an endogenous IL-10 producer. The NK sensitivity in vitro of W31T-H, a high IL-10-producer clone, was suppressed downward to the equivalen t level of W31 cells pretreated with exogenous rhIL-10. The decreased NK-sensitivity of W31T-H cells was further confirmed by in vivo Winn a ssay, in which nude mice challenged with W31T-H cells and rat NK cells together developed tumors, whereas nude mice challenged with W31T-L, a minimal-IL-10 producer clone, and NK cells did not. Since neither ex ogenous nor endogenous IL-10 affected the proliferation of W31 cells, the data indicated that W31T-H cells could evade the NK-cell-mediated immune response in vivo. Taken together, our data reveal a novel mecha nism for an IL-10-mediated escape of tumor cells from host immune syst em by NK cells. (C) 1998 Academic Press.