Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor

Blood. 2006 Feb 15;107(4):1491-6. doi: 10.1182/blood-2005-04-1684. Epub 2005 Oct 25.


The poliovirus receptor CD155 and its family member CD112 (nectin-2) are the ligands for the activating cell-surface receptor DNAM-1 on CD8+ T cells and natural killer (NK) cells. Here, we demonstrate that, whereas the RMA tumor grew in syngeneic mice, DNAM-1 ligand-transduced RMA was rejected, in which CD8+ T cells and NK cells played an essential role. Importantly, CD8+ memory cytotoxic T cells to parental RMA were generated in these mice. We found that DNAM-1 was also expressed on CD8alpha+, rather than CD8alpha-, dendritic cells (DCs). Cross-linking DNAM-1 induced maturation of CD8alpha+ DCs. Antigen presentation by these stimulated DCs drove Th1 cells. Moreover, the rejection of DNAM-1 ligand-transduced RMA was canceled in CD4+ T-cell-depleted and major histocompatibility complex class II-deficient mice. Taken together, these results suggest that DNAM-1 ligands stimulate innate immunity by CD8alpha+ DCs as well as NK cells, which efficiently prime cell-mediated tumor-specific immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Immunologic Memory*
  • Ligands
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology*
  • Receptors, Virus / immunology*


  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • Ligands
  • Membrane Proteins
  • Receptors, Virus
  • poliovirus receptor