An essential role for tumor necrosis factor in natural killer cell-mediated tumor rejection in the peritoneum.
An essential role for tumor necrosis factor in natural killer cell-mediated tumor rejection in the peritoneum.
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DOI：
10.1084/jem.188.9.1611
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发表时间：
1998-11-02
期刊：
影响因子：
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通讯作者：
Sedgwick JD
中科院分区：
文献类型：
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作者：
Smyth MJ;Kelly JM;Baxter AG;Körner H;Sedgwick JD
自然杀伤（NK）细胞被认为是对抗肿瘤的第一道防线，特别是主要组织相容性复合体（MHC）I类变异体。我们已经在缺乏穿孔素的C57 BL/6（B6）小鼠中证实，未致敏小鼠中MHC I类-RMA-S肿瘤细胞的腹膜生长是由CD 3-NK1.1+细胞介导的穿孔素依赖性细胞毒性控制的。此外，我们证明，B6小鼠缺乏肿瘤坏死因子（TNF）也显着缺陷，在他们的排斥反应的RMA-S，尽管事实上，RMA-S是不敏感的TNF在体外和脾NK细胞从B6和TNF-缺陷小鼠同样裂解对RMA-S。与B6或穿孔素缺陷小鼠相比，在用RMA-S或RM-1（一种B6 MHC I类前列腺癌）攻击的TNF缺陷小鼠中，NK细胞向腹膜的募集被废除。TNF缺陷小鼠的NK细胞向腹膜的迁移减少与这些小鼠中NK细胞对肿瘤的反应缺陷相关。相比之下，缺乏TNF并不影响肽特异性细胞毒性T淋巴细胞介导的排斥肿瘤从预免疫小鼠的腹膜。总的来说，这些数据表明，NK细胞提供穿孔素是腹膜中I类肿瘤排斥反应的主要效应物，TNF对它们向腹膜的募集特别关键。
Natural killer (NK) cells are thought to provide the first line of defence against tumors, particularly major histocompatibility complex (MHC) class I− variants. We have confirmed in C57BL/6 (B6) mice lacking perforin that peritoneal growth of MHC class I− RMA-S tumor cells in unprimed mice is controlled by perforin-dependent cytotoxicity mediated by CD3− NK1.1+ cells. Furthermore, we demonstrate that B6 mice lacking tumor necrosis factor (TNF) are also significantly defective in their rejection of RMA-S, despite the fact that RMA-S is insensitive to TNF in vitro and that spleen NK cells from B6 and TNF-deficient mice are equally lytic towards RMA-S. NK cell recruitment into the peritoneum was abrogated in TNF-deficient mice challenged with RMA-S or RM-1, a B6 MHC class I− prostate carcinoma, compared with B6 or perforin-deficient mice. The reduced NK cell migration to the peritoneum of TNF-deficient mice correlated with the defective NK cell response to tumor in these mice. By contrast, a lack of TNF did not affect peptide-specific cytotoxic T lymphocyte–mediated rejection of tumor from the peritoneum of preimmunized mice. Overall, these data show that NK cells delivering perforin are the major effectors of class I− tumor rejection in the peritoneum, and that TNF is specifically critical for their recruitment to the peritoneum.