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Selective depletion of nk cell activity in vivo and its effect on the growth of NK‐sensitive and nk‐resistant tumor cell variants
Author(s) -
Kawase Ichiro,
Urdal David L.,
Brooks Colin G.,
Henney Christopher S.
Publication year - 1982
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910290513
Subject(s) - cytotoxic t cell , in vivo , in vitro , cytotoxicity , natural killer cell , biology , microbiology and biotechnology , cell culture , lymphokine activated killer cell , cell , antiserum , immunology , antibody , chemistry , interleukin 21 , biochemistry , genetics
Intravenous injection of rabbit anti‐asialo‐GM 1 serum, an antiserum previously shown to eliminate splenic natural killer (NK) activity in vitro , profoundly depressed NK activity in CBA, DBA/2 and BALB/c nu/nu mice. The effect on NK activity was selective, as treatment of mice with anti‐asialo‐GM 1 serum did not affect the development of other cytotoxic cells including cytotoxic macrophages following injection of poly 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 NK‐resistant (cl 27av) subline of the murine lymphoma L5178Y. Initial studies showed that cl 27v‐IC2 cells were at least 100 times less tumorigenic than were cl 27av cells in both syngeneic DBA/2 mice and BALB/c nu/nu mice. In addition, treatment of DBA/2 mice with poly I:C, which boosted NK activity, markedly depressed the growth of cl 27v‐IC2 cells, but not of cl 27av cells. On the other hand, treatment of DBA/2 mice and BALB/c nu/nu mice with antiasialo‐GM1 1 serum led to a marked increase in tumorigenicity of cl 27v‐IC2 cells, but had no effect on the tumorigenicity of cl 27av cells. In addition, the protection against cl 27v‐IC2 growth afforded by poly‐I:C treatment was abrogated by injection of anti‐asialo‐GM 1 serum. The possibility that the effects observed were caused by binding of the injected antibodies to the tumor cells was minimized by: (1) using a clone of tumor cells (cl 27v‐IC2) that lacks chemically detectable asialo‐GM 1 , and (2) pre treating animals with anti‐asialo‐GM 1 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 1 serum is a method which would be generally applicable to studying the role of NK cells in disease processes.