The Journal of Experimental Medicine
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Published 1 July 2002. doi:10.1084/jem.20020092
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*3-METHYLCHOLANTHRENE
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© Rockefeller University Press, 0022-1007/2002/7/119/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 1, July 1, 2002 119-127

A Critical Role for Natural Killer T Cells in Immunosurveillance of Methylcholanthrene-induced Sarcomas

Nadine Y. Crowe1, Mark J. Smyth2 and Dale I. Godfrey1

1 Department of Pathology and Immunology, Monash University Medical School, Melbourne, Victoria 3181, Australia
2 Cancer Immunology, Trescowthick Laboratories, Peter MacCallum Cancer Institute, Melbourne, Victoria 3002, Australia

Address correspondence to Dale Godfrey, Monash University Medical School, Department of Pathology and Immunology, Commercial Rd., Prahran 3181, Victoria, Australia. Phone: 613-9903-0075; Fax: 613-9903-0018; E-mail: dale.godfrey{at}med.monash.edu.au

Natural killer (NK) T cells initiate potent antitumor responses when stimulated by exogenous factors such as interleukin (IL)-12 or {alpha}-galactosylceramide ({alpha}-GalCer), however, it is not clear whether this reflects a physiological role for these cells in tumor immunity. Through adoptive transfer of NK T cells from wild-type to NK T cell–deficient (T cell receptor [TCR] J{alpha}281-/-) mice, we demonstrate a critical role for NK T cells in immunosurveillance of methylcholanthrene (MCA)-induced fibrosarcomas, in the absence of exogenous stimulatory factors. Using the same approach with gene-targeted and/or antibody-depleted donor or recipient mice, we have shown that this effect depends on CD1d recognition and requires the additional involvement of both NK and CD8+ T cells. Interferon-{gamma} production by both NK T cells and downstream, non-NK T cells, is essential for protection, and perforin production by effector cells, but not NK T cells, is also critical. The protective mechanisms in this more physiologically relevant system are distinct from those associated with {alpha}-GalCer–induced, NK T cell–mediated, tumor rejection. This study demonstrates that, in addition to their importance in tumor immunotherapy induced by IL-12 or {alpha}-GalCer, NK T cells can play a critical role in tumor immunosurveillance, at least against MCA-induced sarcomas, in the absence of exogenous stimulation.

Key Words: rodent • NK T cells • NK cells • tumor immunity • methylcholanthrene


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