Induction of antigen-dependent interleukin-12 production by negatively charged liposomes encapsulating antigens

Vaccine. 2004 Sep 3;22(25-26):3503-9. doi: 10.1016/j.vaccine.2004.01.071.

Abstract

The aim of this study was to clarify the mechanism of adjuvant action induced by negatively charged liposomes composed of phosphatidylserine (PS-liposomes). Coculture of mouse splenic adherent cells with ovalbumin (OVA)-specific Th1 clone (42-6A) cells in the presence of PS-liposomes encapsulating OVA resulted in high levels of IL-12 and IFN-gamma productions compared with those of positively charged or neutral liposomes. IL-12 and IFN-gamma productions were dose-dependent on antigens in PS-liposomes. The expression of CD40L on 42-6A cells was enhanced by treatment with PS-liposomes encapsulating OVA. IL-12 production, but not IFN-gamma, was completely inhibited by the addition of anti-CD40L mAb. These results indicate that PS-liposomes encapsulating antigens could enhance antigen-dependent IL-12 production through the interaction between CD40 on macrophage/dendritic cells and CD40L on 42-6A cells.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • CD40 Antigens / administration & dosage*
  • CD40 Antigens / immunology*
  • Cell Adhesion
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Drug Carriers
  • Flow Cytometry
  • Immunoglobulin G / analysis
  • Immunoglobulin G / biosynthesis
  • Interferon-gamma / analysis
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis*
  • Liposomes
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Phosphatidylserines
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / cytology
  • Th1 Cells / immunology

Substances

  • Adjuvants, Immunologic
  • CD40 Antigens
  • Drug Carriers
  • Immunoglobulin G
  • Liposomes
  • Phosphatidylserines
  • RNA, Messenger
  • Interleukin-12
  • Interferon-gamma
  • Ovalbumin