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J. Exp. Med.,
Volume 188, Number 9, November 2, 1998 1611-1619
By



From the * Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Victoria
3084, Australia; and the Natural killer (NK) cells are thought to provide the first line of defence against tumors, particularly major histocompatibility complex (MHC) class I
Centenary Institute of Cancer Medicine and Cell Biology, Royal Prince
Alfred Hospital, Sydney, New South Wales 2050, Australia
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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