NK cells modulate MHC class I expression on tumor cells and their susceptibility to lysis

Cytotoxicity and production of cytokines are two important functions of NK cells. These two different NK functions were studied in a syngeneic rat mod el in relation to MHC class I expression. We focussed on the mechanism by w hich NK cells modulate MHC class I expression on target cells and how this interferes with NK cell-mediated lysis. Using transfection experiments an i nhibitory role on NK cell cytotoxicity for expression of target cells of RT 1.A, rat MHC class I, was found. Co-culturing syngeneic tumor cells and NK cells resulted in enhanced MHC class I expression on the surviving tumor ce ll fraction, which was less susceptible to NK lysis. Increased tumor cell M HC class I was due to production of a soluble factor by NK cells, most like ly interferon gamma. The regulatory function of NK cells shows here, that t he enhancing of MHC class I expression on tumor cells in vitro and in vivo, results in downregulation of their target cell killing, but at the same ti me may facilitate the cytotoxic T cell function.