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An Essential Role for Tumor Necrosis Factor in Natural Killer Cell-mediated Tumor Rejection in the Peritoneum

Citation

Smyth, MJ and Kelly, JM and Baxter, AG and Korner, H and Sedgwick, JD, An Essential Role for Tumor Necrosis Factor in Natural Killer Cell-mediated Tumor Rejection in the Peritoneum, The Journal of Experimental Medicine, 188, (9) pp. 1611-1619. ISSN 0022-1007 (1998) [Refereed Article]

DOI: doi:10.1084/jem.188.9.1611

Abstract

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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Korner, H (Professor Heinrich Korner)
ID Code:72441
Year Published:1998
Web of Science® Times Cited:101
Deposited By:Research Division
Deposited On:2011-08-26
Last Modified:2011-08-29
Downloads:0

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