Selective depletion of nk cell activity in vivo and its effect on the growth of NK-sensitive and nk-resistant tumor cell variants

✍ Scribed by Ichiro Kawase; David L. Urdal; Colin G. Brooks; Christopher S. Henney

• Publisher: John Wiley and Sons
• Year: 1982
• Tongue: French
• Weight: 827 KB
• Volume: 29
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910290513

✦ Synopsis

Intravenous injection of rabbit anti-asialo-GM, serum, M antiserum previously shown to eliminate splenic natural killer (NK) activity in vitro, profoundly depressed NK activity in CBA, DBN2 and BALBIc nu/nu mice. The effect on N K activity was selective, as treatment of mice with anti-asialo-GM, serum did not affect the develop ment of other cytotoxic cells including cytotoxic macrophages following injection of p l y I:C, or cytotoxic T cells in response to allogeneic cells. The role of NK cells in controlling tumor cell growth was investigated using an NK-sensitive (cl 27v-IC2) and an subline of the murine lymphoma l5178Y. Initial studies showed that cl 27v-IC2 cells were at least 100 times less tumorigenic than were c l 27av cells in both syngeneic DBAl2 mice and BALBlc nuhu mice. In addition, treatment of DBN2 mice with poly I:C, which boosted NK activity, markedly depressed the growth of c l 27v-IC2 cells, but not of c l 27av cells. On the other hand, treatment of DBAl2 mice and BALBlc nuhu mice with antiasialo-GM, serum led to a marked increase in tumorigenicity of cl27v-1 CZ cells, but had no effect on the tumorigenicity of cl27av cells. In addition, the protection against cl27v-IC2 growth afforded by poly-l:C treatment was abrogated by injection of anti-asialo-GM, serum. The possibility that the effects observed were caused by binding of the injected antibodies to the tumor cells was minimized by: ( I ) using a clone of tumor cells (cI27v-IC2) that lacks chemically detectable asialo-GM,, and (2) pretreating animals with anti-asialo-GM, rather than administering antiserum and tumor cells concurrently. These studies provided compelling evidence that NK cells could play an active role in controlling tumor growth. Selective depletion of NK activity by injection of antiasialo-GM, serum i s a method which would be generally applicable to studying the role of N K cells in disease processes.