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Interleukin‐12 induces cytotoxic NK1 + αβ T cells in the lungs of euthymic and athymic mice
Author(s) -
ANZAI R.,
SEKI S.,
OGASAWARA K.,
HASHIMOTO W.,
SUGIURA K.,
SATO M.,
KUMAGAI K.,
TAKEDA K.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.d01-638.x
Subject(s) - cytotoxic t cell , cytotoxicity , interleukin 12 , cd8 , interleukin 21 , microbiology and biotechnology , interferon gamma , biology , major histocompatibility complex , immunology , interferon type ii , population , cytokine , antigen , in vitro , medicine , biochemistry , environmental health
We recently reported that interleukin‐12 (IL‐12) stimulated hepatic NK1.1 Ag + αβ T cells with intermediate T‐cell receptor (TCR; NK1 + TCR int cells) and enhanced their NK1 expression (NK1 high TCR int ), and that these cells acquire strong major histocompatibility complex (MHC) unrestricted cytotoxicity in C57BL/6 mice, both +/+ and nu/nu . In the present study, we find that although murine lung normally has few NK1 + TCR int cells, NK1 high TCR int cells are induced in +/+ and nu/nu mice after systemic administration of IL‐12; these cells exhibit strong MHC unrestricted cytotoxicity against NK‐sensitive and ‐resistant targets. A small number of NK1 high TCR int cells was also found in peripheral blood after increased amounts of IL‐12 were administered. Cytotoxicity tests in vitro revealed that the cytotoxic activity of the lung mononuclear cells (MNC) of C57BL/6 mice induced by IL‐12 was abrogated by the depletion of either NK1 + or CD3 + cells, but not of CD8 + cells, as reportedly was the case of hepatic MNC, suggesting that NK1 high TCR int cells are an antimetastatic population not only in the liver but also in the lung of mice. IL‐12 injection into mice markedly elevates serum interferon‐γ (IFN‐γ) levels. However, although IL‐12‐induced cytotoxicity of NK1 high TCR int cells was significantly reduced by anti‐IFN‐γ antibody injection (which decreased serum IFN‐γ to an undetectable level), the appearance of NK1 high TCR int cells in the lung and liver was not so affected. These results suggest that IFN‐γ is an important mediator of the cytotoxicity of NK1 high TCR int cells but is not an essential factor for induction of these cells. We also added data showing that IL‐12 has a broad antimetastatic effect against various liver and lung metastatic tumours intravenously injected into several strains of mice, including NK‐deficient bg/bg mice. It can be considered that, in addition to NK cells, CD8 + cytotoxic T cells and γδ T cells, NK1 + TCR int cells can be categorized as one of the cytotoxic effector populations. These novel type cells distinct from regular T cells may play an important role in monitoring intra‐ and perivascular areas.