Invariant NKT cells induce plasmacytoid dendritic cell (DC) cross-talk with conventional DCs for efficient memory CD8+ T cell induction

J Immunol. 2013 Jun 1;190(11):5609-19. doi: 10.4049/jimmunol.1300033. Epub 2013 Apr 29.


A key goal of vaccine immunotherapy is the generation of long-term memory CD8(+) T cells capable of mediating immune surveillance. We discovered a novel intercellular pathway governing the development of potent memory CD8(+) T cell responses against cell-associated Ags that is mediated through cross-presentation by XCR1(+) dendritic cells (DCs). Generation of CD8(+) memory T cells against tumor cells pulsed with an invariant NKT cell ligand depended on cross-talk between XCR1(+) and plasmacytoid DCs that was regulated by IFN-α/IFN-αR signals. IFN-α production by plasmacytoid DCs was stimulated by an OX40 signal from the invariant NKT cells, as well as an HMGB1 signal from the dying tumor cells. These findings reveal a previously unknown pathway of intercellular collaboration for the generation of tumor-specific CD8(+) memory T cells that can be exploited for strategic vaccination in the setting of tumor immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Communication / immunology*
  • Cell Line, Tumor
  • Chemotaxis / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Immunologic Memory*
  • Interferon Type I / immunology
  • Interferon Type I / metabolism
  • Interleukin-12 / biosynthesis
  • Ligands
  • Mice
  • Natural Killer T-Cells / immunology*
  • Neoplasms / immunology
  • Signal Transduction


  • Interferon Type I
  • Ligands
  • Interleukin-12