Cloned lines of natural killer cells

Abstract

A class of cytotoxic effector cells has recently been discovered^1,2 in normal and immunodeficient nude mice that lyse a wide range of targets of both tumour and non-tumour origin. Unlike other lymphocytes, these natural killer (NK) cells are present at high levels without prior priming and have no immunological memory. Because NK cells act without prior sensitization, they could have a crucial role in immunosurveillance, providing a first defence against arising neoplastic cells. The question of NK-cell specificity is not well understood; results so far suggest that they may recognize specific antigens on their targets. Thus unlabelled competitor cells can inhibit the cytotoxic reaction of NK cells³. Furthermore, target–effector binding can be inhibited by isolated target structures⁴. Experiments in which the lysis of mouse and human NK-sensitive targets was competitively inhibited with target suggested that the targets recognized by NK cells are not common ones. To study this important aspect, permanent lines and clones of NK cells have been established in vitro. I report here a successful attempt to do this, and show that sublines display the same specificity spectrum as NK cells from normal cells even after recloning. This proves that antigen receptors on NK cells are not clonally distributed but leaves open the two possibilities that NK cells either recognize common structures on NK-sensitive targets or carry many receptors each with a different specificity. Cell-surface markers of NK lines distinguished them from allospecific thymus-derived lymphocyte cell lines through their lack of Lyt-1 and Lyt-2 antigen.