| First Author | Smyth MJ | Year | 1998 |
| Journal | J Exp Med | Volume | 188 |
| Issue | 9 | Pages | 1611-9 |
| PubMed ID | 9802973 | Mgi Jnum | J:50764 |
| Mgi Id | MGI:1309702 | Doi | 10.1084/jem.188.9.1611 |
| Citation | Smyth MJ, et al. (1998) An essential role for tumor necrosis factor in natural killer cell-mediated tumor rejection in the peritoneum. J Exp Med 188(9):1611-9 |
| abstractText | 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. |
