The Journal of Experimental Medicine
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Published 2 September 2003. doi:10.1084/jem.20021282
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© Rockefeller University Press, 0022-1007/2003/9/747 $5.00
The Journal of Experimental Medicine, Volume 198, Number 5, 747-755

The Distinct Contributions of Murine T Cell Receptor (TCR){gamma}{delta}+ and TCR{alpha}ß+ T Cells to Different Stages of Chemically Induced Skin Cancer

Michael Girardi1, Earl Glusac1, Renata B. Filler1, Scott J. Roberts1, Iva Propperova3, Julia Lewis1, Robert E. Tigelaar1,2 and Adrian C. Hayday4

1 Department of Dermatology and the Yale Skin Diseases Research Core Center, Yale University, New Haven, CT 06520
2 Section of Immunobiology, Yale University, New Haven, CT 06520
3 Department of Dermatology and Venereology, Motal University Hospital, 150 06 Prague 5, Czech Republic
4 Peter Gorer Department of Immunobiology, Guy's King's St. Thomas' School of Medicine, Guy's Hospital, SE1 9RT London, United Kingdom

Address correspondence to Adrian Hayday, Guy's King's St. Thomas' School of Medicine, Peter Gorer Department of Immunobiology, 3rd Floor, New Guy's House, Guy's Hospital, SE1 9RT London, United Kingdom. Phone: 44-20-7955-4355; Fax: 44-20-7955-8894; email: adrian.hayday{at}kcl.ac.uk

Epithelial tissues in which carcinomas develop often contain systemically derived T cell receptor (TCR){alpha}ß+ cells and resident intraepithelial lymphocytes that are commonly enriched in TCR{gamma}{delta}+ cells. Recent studies have demonstrated that {gamma}{delta} cells protect the host against chemically induced cutaneous malignancy, but the role of {alpha}ß T cells has been enigmatic, with both protective and tumor-enhancing contributions being reported in different systems. This study aims to clarify the contributions of each T cell type to the regulation of squamous cell carcinoma induced in FVB mice by a two-stage regimen of 7,12-dimethylbenz[a]anthracene initiation followed by repetitive application of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate. This protocol permits one to monitor the induction of papillomas and the progression of those papillomas to carcinomas. The results show that whereas {gamma}{delta} cells are strongly protective, the nonredundant contributions of {alpha}ß T cells to the host's protection against papillomas are more modest. Furthermore, at both high and low doses of carcinogens, {alpha}ß T cells can contribute to rather than inhibit the progression of papillomas to carcinomas. As is likely to be the case in humans, this study also shows that the contribution of T cells to tumor immunosurveillance is regulated by modifier genes.

Key Words: carcinogenesis • squamous cell carcinoma • TCR {gamma}{delta} • TCR {alpha}ß • immunogenetics


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