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

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 c...

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Autores principales: Smyth, Mark J., Kelly, Janice M., Baxter, Alan G., Körner, Heinrich, Sedgwick, Jonathon D.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212521/
https://www.ncbi.nlm.nih.gov/pubmed/9802973
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author Smyth, Mark J.
Kelly, Janice M.
Baxter, Alan G.
Körner, Heinrich
Sedgwick, Jonathon D.
author_facet Smyth, Mark J.
Kelly, Janice M.
Baxter, Alan G.
Körner, Heinrich
Sedgwick, Jonathon D.
author_sort Smyth, Mark J.
collection PubMed
description 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.
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spelling pubmed-22125212008-04-16 An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum Smyth, Mark J. Kelly, Janice M. Baxter, Alan G. Körner, Heinrich Sedgwick, Jonathon D. J Exp Med Articles 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. The Rockefeller University Press 1998-11-02 /pmc/articles/PMC2212521/ /pubmed/9802973 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Smyth, Mark J.
Kelly, Janice M.
Baxter, Alan G.
Körner, Heinrich
Sedgwick, Jonathon D.
An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum
title An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum
title_full An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum
title_fullStr An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum
title_full_unstemmed An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum
title_short An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum
title_sort essential role for tumor necrosis factor in natural killer cell–mediated tumor rejection in the peritoneum
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212521/
https://www.ncbi.nlm.nih.gov/pubmed/9802973
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