Regulation of cutaneous malignancy by gammadelta T cells

Research output: Contribution to journalArticle

Authors

  • M Girardi
  • D E Oppenheim
  • J M Lewis
  • E Glusac
  • R Filler
  • P Hobby
  • B Sutton
  • R E Tigelaar
  • A C Hayday

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)605-9
Number of pages5
JournalScience
Volume294
Issue number5542
Publication statusPublished - 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