Regulation of cutaneous malignancy by γδ T cells

M Girardi, DE Oppenheim, CR Steele, JM Lewis… - Science, 2001 - science.org
M Girardi, DE Oppenheim, CR Steele, JM Lewis, E Glusac, R Filler, P Hobby, B Sutton…
Science, 2001science.org
The localization of γδ T cells within epithelia suggests that these cells may contribute to the
down-regulation of epithelial malignancies. We report that mice lacking γδ 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 …
The localization of γδ T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking γδ 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+ γδ 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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