Interferon-induced autologous reactivity of human natural killer cells.

Abstract

The reactivity of human natural killer (NK) cells against normal autologous target cells was studied. The following major observations were made: (i) non-stimulated NK cells did not lyse autologous target cells, although allogeneic cells were killed to some extent. However, treatment of effector cells with interferon (IFN) resulted in induction of autologous cytotoxicity, and both autologous and allogeneic fibroblast targets were efficiently killed without preference. This was demonstrated both with unfractionated lymphocytes and with effector cells highly enriched in large granular lymphocytes (LGL). (ii) NK cells bound to autologous cells as efficiently as to allogeneic cells. The cells binding to autologous cells were able to lyse K562 cells, demonstrating their NK nature. After stimulation with IFN autologous cells were also killed. (iii) The exemption from autologous cytotoxicity by the non-stimulated NK cells seemed to result from a block at a post-binding stage, and there did not appear to be any need for accessory cells in the induction of autologous reactivity by IFN treatment of the LGLs. The results thus point to important post-binding-stage regulatory mechanisms saving normal cells from the cytotoxic action of circulating NK cells and may help to understand the suggested role of NK cells in certain autoimmune diseases.