Enhancement of BCG-induced Th1 immune response through Vgamma9Vdelta2 T cell activation with non-peptidic drugs

Vaccine. 2007 Jan 22;25(6):1023-9. doi: 10.1016/j.vaccine.2006.09.070. Epub 2006 Oct 9.

Abstract

Since drug-activated gammadelta T cells promote dendritic cell (DC) maturation, we analyzed the effect of combining gammadelta T cell specific drugs with BCG in vitro. BCG-induced DC maturation was increased by bromohydrin-pirophosphate (BrHPP) or zoledronate (Zol)-activated gammadelta T cells. Specifically, the co-culture with activated Vgamma9Vdelta2 T cells with BCG-infected DC resulted in a significant increase of the expression of CD80, CD86, CD40 and CD25 molecules on DC. Moreover, DC were able to produce increased levels of TNF-alpha and synthesize ex novo IL-15 without altering the IL-10/IL-12 immunoregulatory pathway. Finally, the Th1 immunity induced by BCG-infected DC on naïve CD4 T cells was increased by gammadelta T cell activation with BrHpp or Zol. These data indicate that gammadelta T cell triggering drugs could be used to enhance the BCG induced Th1 immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / pharmacology*
  • CD4-Positive T-Lymphocytes / immunology
  • Coculture Techniques
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / microbiology
  • Diphosphonates / pharmacology*
  • Humans
  • Imidazoles / pharmacology*
  • Interleukin-10 / immunology
  • Interleukin-15 / immunology
  • Lymphocyte Activation
  • Mycobacterium bovis / immunology*
  • Mycobacterium tuberculosis / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Tuberculosis Vaccines / immunology
  • Tuberculosis Vaccines / therapeutic use
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology
  • Zoledronic Acid

Substances

  • Alcohols
  • Diphosphonates
  • Imidazoles
  • Interleukin-15
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tuberculosis Vaccines
  • Tumor Necrosis Factor-alpha
  • bromohydrins
  • Interleukin-10
  • Zoledronic Acid