Enhancement of IFN-gamma production for Th1-cell therapy using negatively charged liposomes containing phosphatidylserine

Vaccine. 2007 Jul 20;25(29):5256-62. doi: 10.1016/j.vaccine.2007.05.037. Epub 2007 Jun 8.

Abstract

We have developed an efficient method of interferon-gamma (IFN-gamma) induction for Th1-cell therapy. OVA (ovalbumin)-specific Th1 clone 42-6A cells cocultured with antigen presenting cells (APCs) from spleen resulted in high levels of OVA-specific IFN-gamma production by the treatment of phosphatidylserine (PS), but not phosphatidic acid (PA), liposomes-encapsulated OVA (OVA-liposomes). The IFN-gamma production was increased in a manner dependent on the PS content of the liposomes and inhibited by the addition of annexin V, a PS binding protein. Furthermore, coadministration of Th1 cells plus OVA-liposomes in mice strikingly enhanced IFN-gamma levels in serum and in spleen cells compared with that of Th1 cells plus OVA. In addition, serum levels of IL-12 p70 increased and ongoing OVA-specific IgE immune response was dramatically attenuated. These results first suggest that antigen delivery using negatively charged liposomes containing PS is very useful for the enhancement of IFN-gamma production in Th1-cell therapy.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Immunoglobulin E / blood
  • Immunologic Factors / immunology*
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / blood
  • Interleukin-12 / blood
  • Liposomes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Ovalbumin / immunology
  • Phosphatidylserines / immunology*
  • Th1 Cells / immunology*

Substances

  • Immunologic Factors
  • Liposomes
  • Phosphatidylserines
  • Interleukin-12
  • Immunoglobulin E
  • Interferon-gamma
  • Ovalbumin