Cutting edge: a potent adjuvant effect of ligand to receptor activator of NF-kappa B gene for inducing antigen-specific CD8+ T cell response by DNA and viral vector vaccination

J Immunol. 2003 Dec 15;171(12):6344-8. doi: 10.4049/jimmunol.171.12.6344.

Abstract

The ligand to receptor activator of NF-kappaB (RANK-L)/RANK interaction has been implicated in CD40 ligand/CD40-independent T cell priming by dendritic cells. In this report, we show that the coadministration of the RANK-L gene with a Trypanosoma cruzi gene markedly enhances the induction of Trypanosoma Ag-specific CD8(+) T cells and improves the DNA vaccine efficacy. A similarly potent adjuvant effect of the RANK-L gene on the induction of Ag-specific CD8(+) T cells was also observed when recombinant influenza virus expressing murine malaria Ag was used as an immunogen. In contrast, the coadministration of the CD40L gene was not effective in these systems. Our results demonstrated, for the first time, the potent immunostimulatory effect of the RANK-L gene to improve the CD8(+) T cell-mediated immunity against infectious agents.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / biosynthesis
  • Adjuvants, Immunologic / genetics
  • Animals
  • CD40 Ligand / biosynthesis
  • CD40 Ligand / genetics
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Carrier Proteins / administration & dosage*
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Cell Line
  • Cell Line, Tumor
  • Chagas Disease / immunology
  • Chagas Disease / mortality
  • Chagas Disease / prevention & control
  • Epitopes, T-Lymphocyte / administration & dosage
  • Epitopes, T-Lymphocyte / biosynthesis
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Genetic Vectors
  • Glycoproteins / metabolism*
  • Humans
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Membrane Glycoproteins / administration & dosage*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Neuraminidase / administration & dosage
  • Neuraminidase / biosynthesis
  • Neuraminidase / genetics
  • Neuraminidase / immunology
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Tumor Necrosis Factor
  • Trypanosoma cruzi / genetics
  • Trypanosoma cruzi / immunology
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / genetics
  • Vaccines, Combined / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology

Substances

  • Adjuvants, Immunologic
  • Carrier Proteins
  • Epitopes, T-Lymphocyte
  • Glycoproteins
  • Influenza Vaccines
  • Membrane Glycoproteins
  • NF-kappa B
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Tnfrsf11a protein, mouse
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Vaccines, Combined
  • Vaccines, DNA
  • Vaccines, Synthetic
  • CD40 Ligand
  • trans-sialidase
  • Neuraminidase