Anzai R, Seki S, Ogasawara K, Hashimoto W, Sugiura K, Sato M, Kumagai K, Takeda K
Department of Microbiology, Tohoku University School of Dentistry, Japan.
Immunology. 1996 May;88(1):82-9. doi: 10.1046/j.1365-2567.1996.d01-638.x.
We recently reported that interleukin-12 (IL-12) stimulated hepatic NK1.1 Ag+ alpha beta T cells with intermediate T-cell receptor (TCR; NK1+ TCRint cells) and enhanced their NK1 expression (NK1high TCRint), 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+ TCRint cells, NK1high TCRint 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 NK1high TCRint 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 NK1high TCRint 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-gamma (IFN-gamma) levels. However, although IL-12-induced cytotoxicity of NK1high TCRint cells was significantly reduced by anti-IFN-gamma antibody injection (which decreased serum IFN-gamma to an undetectable level), the appearance of NK1high TCRint cells in the lung and liver was not so affected. These results suggest that IFN-gamma is an important mediator of the cytotoxicity of NK1high TCRint 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 gamma delta T cells, NK1+ TCRint 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.
我们最近报道，白细胞介素-12（IL-12）刺激具有中间型T细胞受体（TCR；NK1+TCRint细胞）的肝NK1.1 Ag+αβT细胞，并增强其NK1表达（NK1high TCRint），并且这些细胞在C57BL/6小鼠（包括+/+和nu/nu小鼠）中获得强大的主要组织相容性复合体（MHC）非限制性细胞毒性。在本研究中，我们发现，虽然小鼠肺中通常很少有NK1+TCRint细胞，但在全身给予IL-12后，+/+和nu/nu小鼠中可诱导出NK1high TCRint细胞；这些细胞对NK敏感和抗性靶标表现出强大的MHC非限制性细胞毒性。在给予增加量的IL-12后，外周血中也发现了少量NK1high TCRint细胞。体外细胞毒性试验显示，IL-12诱导的C57BL/6小鼠肺单核细胞（MNC）的细胞毒性活性可通过去除NK1+或CD3+细胞而被消除，但去除CD8+细胞则不能，据报道肝MNC也是如此，这表明NK1high TCRint细胞不仅在小鼠肝脏中，而且在肺中都是抗转移细胞群体。向小鼠注射IL-12可显著提高血清干扰素-γ（IFN-γ）水平。然而，虽然注射抗IFN-γ抗体（可将血清IFN-γ降低至检测不到的水平）可显著降低IL-12诱导的NK1high TCRint细胞的细胞毒性，但肺和肝中NK1high TCRint细胞的出现并未受到如此大的影响。这些结果表明，IFN-γ是NK1high TCRint细胞细胞毒性的重要介质，但不是诱导这些细胞的必需因子。我们还补充了数据，表明IL-12对静脉注射到包括NK缺陷型bg/bg小鼠在内的几种小鼠品系中的各种肝和肺转移瘤具有广泛的抗转移作用。可以认为，除了NK细胞、CD8+细胞毒性T细胞和γδT细胞外，NK1+TCRint细胞可被归类为细胞毒性效应细胞群体之一。这些不同于常规T细胞的新型细胞可能在监测血管内和血管周围区域中发挥重要作用。
