RESTORATION OF LYTIC FUNCTION IN A HUMAN NATURAL-KILLER-CELL LINE BY GENE TRANSFECTION

NK cells can recognize and lyse target cells without restriction by th e MHC. The molecular interaction responsible for NK cell recognition i s poorly understood. It has been frequently suggested that the loss of beta(2) integrin in immune competent cells may lead to dysfunction du e to inadequate cell-cell interaction. We examined the role of lymphoc yte functional adhesion molecule-1 in the function of a human natural killer leukemia cell line, YT-1. A mutant YT-1(-) cell subclone showed an absence of killing activity against a B lymphoma cell line, compar ed with that against a CD11a/CD18 positive parental cell line, YT-1(+) cells. We found that this loss of cytotoxicity was correlated with la ck of surface expression of CD11a/CD18 molecules due to the mutation o f the CD18 gene. Using gene transfer experiments, we provide strong ev idence demonstrating that CD18 transfection to this mutant NK cell lin e, YT-1(-), restored the surface expression of CD11a/CD18, and this re storation was accompanied by reexpression of cytotoxic function. (C) 1 994 Academic Press, Inc.