Dendritic cells require maturation via CD40 to generate protective antitumor immunity

J Immunol. 1998 Sep 1;161(5):2094-8.

Abstract

A critical role for CD40/CD154 interactions in the generation of protective cell-mediated tumor immunity has been demonstrated previously. Herein, we show that the failure to generate systemic tumor immunity in the absence of CD40/CD154 interactions correlates with an inhibition of Th1-type cytokine production following tumor vaccination. Furthermore, protective antitumor responses can be restored in CD40-deficient mice by the coadministration of CD40+/+ but not CD40-/- dendritic cells (DCs) with tumor Ag, suggesting that CD40 is critical for the maturation and function of DCs in vivo. Finally, we demonstrate that an IL-12-transduced but not a mock-transduced tumor vaccine induces systemic tumor immunity in anti-CD154-treated and CD154-deficient mice. These data suggest that impaired antitumor responses in the absence of CD40/CD154 interactions are the result of a lesion in APC function, namely IL-12 production, and that CD40 plays a critical role in the maturation of DCs in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism
  • CD40 Antigens / physiology*
  • CD40 Ligand
  • Cell Differentiation / immunology
  • Cytokines / biosynthesis
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation*
  • Female
  • Immunization, Passive* / methods
  • Interleukin-12 / pharmacology
  • Ligands
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Sarcoma, Experimental / immunology*
  • Th1 Cells / metabolism
  • Tumor Cells, Cultured

Substances

  • CD40 Antigens
  • Cytokines
  • Ligands
  • Membrane Glycoproteins
  • CD40 Ligand
  • Interleukin-12