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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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NKG2D function protects the host from tumor initiation.
M. J. Smyth, J. Swann, E. Cretney, N. Zerafa, W. M. Yokoyama, and Y. Hayakawa (2005)
J. Exp. Med.
202, 583-588
|Abstract »|Full Text »|PDF »
Costimulation through NKG2D Enhances Murine CD8+ CTL Function: Similarities and Differences between NKG2D and CD28 Costimulation.
M. A. Markiewicz, L. N. Carayannopoulos, O. V. Naidenko, K. Matsui, W. R. Burack, E. L. Wise, D. H. Fremont, P. M. Allen, W. M. Yokoyama, M. Colonna, et al. (2005)
J. Immunol.
175, 2825-2833
|Abstract »|Full Text »|PDF »
MICA Expressed by Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance Plasma Cells Costimulates Pamidronate-Activated {gamma}{delta} Lymphocytes.
S. Girlanda, C. Fortis, D. Belloni, E. Ferrero, P. Ticozzi, C. Sciorati, M. Tresoldi, A. Vicari, T. Spies, V. Groh, et al. (2005)
Cancer Res.
65, 7502-7508
|Abstract »|Full Text »|PDF »
Activation of V{gamma}9V{delta}2 T Cells by NKG2D.
B. Rincon-Orozco, V. Kunzmann, P. Wrobel, D. Kabelitz, A. Steinle, and T. Herrmann (2005)
J. Immunol.
175, 2144-2151
|Abstract »|Full Text »|PDF »
Important Roles for Gamma Interferon and NKG2D in {gamma}{delta} T-Cell-Induced Demyelination in T-Cell Receptor {beta}-Deficient Mice Infected with a Coronavirus.
A. A. Dandekar, K. O'Malley, and S. Perlman (2005)
J. Virol.
79, 9388-9396
|Abstract »|Full Text »|PDF »
The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the cell-surface receptor CRTAM.
K. S. Boles, W. Barchet, T. Diacovo, M. Cella, and M. Colonna (2005)
Blood
106, 779-786
|Abstract »|Full Text »|PDF »
Systemic NKG2D Down-Regulation Impairs NK and CD8 T Cell Responses In Vivo.
K. Wiemann, H.-W. Mittrucker, U. Feger, S. A. Welte, W. M. Yokoyama, T. Spies, H.-G. Rammensee, and A. Steinle (2005)
J. Immunol.
175, 720-729
|Abstract »|Full Text »|PDF »
Accelerated chemically induced tumor development mediated by CD4+CD25+ regulatory T cells in wild-type hosts.
H. Nishikawa, T. Kato, I. Tawara, T. Takemitsu, K. Saito, L. Wang, Y. Ikarashi, H. Wakasugi, T. Nakayama, M. Taniguchi, et al. (2005)
PNAS
102, 9253-9257
|Abstract »|Full Text »|PDF »
T Cells
T cells within epithelia suggests that
these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking 
