Abstract
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.
Original language | English |
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Pages (from-to) | 605-9 |
Number of pages | 5 |
Journal | Science |
Volume | 294 |
Issue number | 5542 |
DOIs | |
Publication status | Published - 19 Oct 2001 |
Keywords
- Amino Acid Sequence
- Animals
- Carcinogens
- Cell Line
- Cytotoxicity, Immunologic
- Dimerization
- Epidermis
- Epithelial Cells
- Histocompatibility Antigens Class I
- Humans
- Immunologic Surveillance
- Ligands
- Membrane Proteins
- Mice
- Mice, Inbred C57BL
- Minor Histocompatibility Antigens
- Molecular Sequence Data
- NK Cell Lectin-Like Receptor Subfamily K
- Protein Conformation
- Protein Folding
- Receptors, Antigen, T-Cell, alpha-beta
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, Immunologic
- Receptors, Natural Killer Cell
- Recombinant Fusion Proteins
- Reverse Transcriptase Polymerase Chain Reaction
- Skin Neoplasms
- T-Lymphocyte Subsets