Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis

Nat Immunol. 2008 Feb;9(2):146-54. doi: 10.1038/ni1556. Epub 2008 Jan 6.


The self-encoded ligands MICA (human) and Rae-1 (mouse) for the cytotoxic lymphocyte activating receptor NKG2D are highly expressed in carcinomas and inflammatory lesions and have been linked to immunosurveillance and graft rejection. However, whether NKG2D ligands have an intrinsic ability to acutely regulate tissue-associated immune compartments is not known. Here we show that epidermis-specific upregulation of Rae-1 induced rapid, coincident and reversible changes in the organization of tissue-resident V(gamma)5V(delta)1 TCRgammadelta+ intraepithelial T cells and Langerhans cells, swiftly followed by epithelial infiltration by unconventional alphabeta T cells. Whereas local V(gamma)5V(delta)1+ T cells limited carcinogenesis, Langerhans cells unexpectedly promoted it. These results provide unique insight into the early phases of tissue immunosurveillance and indicate that acute changes in NKG2D ligands may alone initiate a rapid, multifaceted immunosurveillance response in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / immunology*
  • Epidermis / immunology*
  • Histocompatibility Antigens Class I / metabolism*
  • Immunologic Surveillance*
  • Langerhans Cells / immunology*
  • Ligands
  • Mice
  • Mice, Inbred Strains
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Receptors, Antigen, T-Cell, gamma-delta / analysis
  • Receptors, Immunologic / metabolism
  • Receptors, Natural Killer Cell
  • Skin Neoplasms / immunology*
  • T-Lymphocytes / immunology
  • Up-Regulation


  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • Klrk1 protein, mouse
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell