Regulation of cutaneous malignancy by gammadelta T cells.
The localization of gammadelta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gammadelta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gammadelta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.
Girardi
M
M
Department of Dermatology and Yale Skin Diseases Research Core Center, King's College, London SE1 9RT, UK.
Oppenheim
D E
DE
Steele
C R
CR
Lewis
J M
JM
Glusac
E
E
Filler
R
R
Hobby
P
P
Sutton
B
B
Tigelaar
R E
RE
Hayday
A C
AC
D000595:Amino Acid Sequence; D000818:Animals; D002273:Carcinogens; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D019281:Dimerization; D004817:Epidermis / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007157:Immunologic Surveillance; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011487:Protein Conformation; D017510:Protein Folding; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000139:chemically induced / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D002273:Carcinogens; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; C099187:MHC class I-related chain A; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; C491219:Raet1a protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins; C114735:minor H antigen H60