Regulation of cutaneous malignancy by gammadelta T cells |
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Authors: | Girardi M Oppenheim D E Steele C R Lewis J M Glusac E Filler R Hobby P Sutton B Tigelaar R E Hayday A C |
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Institution: | Department of Dermatology and Yale Skin Diseases Research Core Center, King's College, London SE1 9RT, UK. |
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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. |
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