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Michael Girardi,1*David E. Oppenheim,2*Carrie R. Steele,2Julia M. Lewis,1Earl Glusac,1Renata Filler,1Paul Hobby,3Brian Sutton,3Robert E. Tigelaar,1Adrian C. Hayday2
The localization of T cells within epithelia suggests that
these cells may contribute to the down-regulation of epithelialmalignancies. We report that mice lacking cells are highlysusceptible to multiple regimens of cutaneous carcinogenesis.After
exposure to carcinogens, skin cells expressed Rae-1 andH60, major
histocompatibility complex-related molecules structurallyresembling
human MICA. Each of these is a ligand for NKG2d, areceptor expressed
by cytolytic T cells and natural killer (NK)cells. In vitro,
skin-associated NKG2d+ cells killed skin carcinoma
cells by a mechanism that wassensitive to blocking NKG2d engagement.
Thus, local T cells mayuse evolutionarily conserved proteins to
negatively regulate malignancy.
1 Department of Dermatology and Yale Skin Diseases
Research Core Center,
2 Peter Gorer Department of
Immunobiology, Guy's King's St. Thomas' Medical School,
3 Randall Centre for Molecular Medicine, Guy's Hospital,
King's College, London SE1 9RT, UK.
*
These authors contributed equally to this report.
To whom correspondence should be addressed. E-mail:
adrian.hayday{at}kcl.ac.uk
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Drew M. Pardoll (19 October 2001) Science294 (5542), 534.
[DOI: 10.1126/science.1066284] |Summary »|Full Text »|PDF »
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The Distinct Contributions of Murine T Cell Receptor (TCR){gamma}{delta}+ and TCR{alpha}{beta}+ T Cells to Different Stages of Chemically Induced Skin Cancer.
M. Girardi, E. Glusac, R. B. Filler, S. J. Roberts, I. Propperova, J. Lewis, R. E. Tigelaar, and A. C. Hayday (2003)
J. Exp. Med.
198, 747-755
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Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia.
H. R. Salih, H. Antropius, F. Gieseke, S. Z. Lutz, L. Kanz, H.-G. Rammensee, and A. Steinle (2003)
Blood
102, 1389-1396
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{gamma}{delta} T Cells Provide an Early Source of Interferon {gamma} in Tumor Immunity.
Y. Gao, W. Yang, M. Pan, E. Scully, M. Girardi, L. H. Augenlicht, J. Craft, and Z. Yin (2003)
J. Exp. Med.
198, 433-442
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{gamma}{delta} T cells for immune therapy of patients with lymphoid malignancies.
M. Wilhelm, V. Kunzmann, S. Eckstein, P. Reimer, F. Weissinger, T. Ruediger, and H.-P. Tony (2003)
Blood
102, 200-206
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Human Cytomegalovirus Glycoprotein UL16 Causes Intracellular Sequestration of NKG2D Ligands, Protecting Against Natural Killer Cell Cytotoxicity.
C. Dunn, N. J. Chalupny, C. L. Sutherland, S. Dosch, P.V. Sivakumar, D. C. Johnson, and D. Cosman (2003)
J. Exp. Med.
197, 1427-1439
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C. L Smith, N. Dulphy, M. Salio, and V. Cerundolo (2002)
Br. Med. Bull.
64, 181-200
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Cutting Edge: Tumor Rejection Mediated by NKG2D Receptor-Ligand Interaction Is Dependent upon Perforin.
Y. Hayakawa, J. M. Kelly, J. A. Westwood, P. K. Darcy, A. Diefenbach, D. Raulet, and M. J. Smyth (2002)
J. Immunol.
169, 5377-5381
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Cutting Edge: Murine UL16-Binding Protein-Like Transcript 1: A Newly Described Transcript Encoding a High-Affinity Ligand for Murine NKG2D.
L. N. Carayannopoulos, O. V. Naidenko, D. H. Fremont, and W. M. Yokoyama (2002)
J. Immunol.
169, 4079-4083
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T Cells
T cells within epithelia suggests that
these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking 
