The distinct contributions of murine T cell receptor (TCR)gammadelta+ and TCRalphabeta+ T cells to different stages of chemically induced skin cancer.
Epithelial tissues in which carcinomas develop often contain systemically derived T cell receptor (TCR)alphabeta+ cells and resident intraepithelial lymphocytes that are commonly enriched in TCRgammadelta+ cells. Recent studies have demonstrated that gammadelta cells protect the host against chemically induced cutaneous malignancy, but the role of alphabeta 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 gammadelta cells are strongly protective, the nonredundant contributions of alphabeta T cells to the host's protection against papillomas are more modest. Furthermore, at both high and low doses of carcinogens, alphabeta 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.
Girardi
Michael
M
Department of Dermatology and the Yale Skin Diseases Research Core Center, Yale University, New Haven, CT 065420, USA.
Glusac
Earl
E
Filler
Renata B
RB
Roberts
Scott J
SJ
Propperova
Iva
I
Lewis
Julia
J
Tigelaar
Robert E
RE
Hayday
Adrian C
AC
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000276:immunology; D008099:Liver / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D009367:Neoplasm Staging; D010212:Papilloma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D013997:Time Factors
D002273:Carcinogens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate