Regulation of cutaneous malignancy by gammadelta T cells

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

Research output: Contribution to journalArticlepeer-review

740 Citations (Scopus)

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

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