In vivo gammadelta T cell priming to mycobacterial antigens by primary Mycobacterium tuberculosis infection and exposure to nonpeptidic ligands

Mol Med. 1999 Jul;5(7):471-6.

Abstract

Background: The recognition of phosphorylated nonpeptidic microbial metabolites by Vgamma9Vdelta2 T cells does not appear to require the presence of MHC molecules or antigen processing, permitting rapid responses against microbial pathogens. These may constitute an important area of natural anti-infectious immunity. To provide evidence of their involvement in immune reactivities against mycobacteria, we measured the responsiveness of peripheral blood Vgamma9Vdelta2 T cells in children with primary Mycobacterium tuberculosis (MTB) infections.

Materials and methods: Peripheral blood mononuclear cells from 22 children with MTB infections and 16 positivity of tuberculin (PPD)-negative healthy children were exposed to nonpeptidic antigens in vitro and the reactivity of the Vgamma9Vdelta2 T cell subset with these antigens was determined using proliferation and cytokine assays. Also, responses of gammadelta T cells from rhesus monkeys stimulated with phosphoantigens in vivo were measured.

Results: The Vgamma9Vdelta2 T cell responses were highly increased in infected children in comparison with age-matched controls. This augmented Vgamma9Vdelta2 T cell reactivity subsided after successful antibiotic chemotherapy, suggesting that persistent exposure to mycobacterial antigens is required for the maintenance of gammadelta T cell activation in vivo. The in vivo reactivity of Vgamma9Vdelta2 T cells to phosphoantigens was also analyzed in a rhesus monkey model system. Intravenous injections of phosphoantigens induced an activated state of simian Vgamma9Vdelta2 T cells which decreased after 2 months, i.e., with a time course similar to that seen in MTB-infected children.

Conclusions: The increased reactivity of Vgamma9Vdelta2 T cells to phosphoantigens appears to be dependent on constant antigenic exposure. Consequently, the assessment of Vgamma9Vdelta2 responses may be useful for monitoring the efficacy of antimycobacterial therapies.

Publication types

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

MeSH terms

  • Animals
  • Antigens / pharmacology*
  • Antigens, Bacterial / immunology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Diphosphates / pharmacology
  • Female
  • Hemiterpenes*
  • Humans
  • Infant
  • Interferon-gamma / metabolism
  • Ligands
  • Macaca mulatta
  • Male
  • Mycobacterium tuberculosis / immunology*
  • Organophosphorus Compounds / pharmacology
  • Receptors, Antigen, T-Cell, gamma-delta / drug effects
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Sugar Phosphates / pharmacology
  • T-Lymphocytes / drug effects*
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens
  • Antigens, Bacterial
  • Diphosphates
  • Hemiterpenes
  • Ligands
  • Organophosphorus Compounds
  • Receptors, Antigen, T-Cell, gamma-delta
  • Sugar Phosphates
  • Tumor Necrosis Factor-alpha
  • isopentenyl pyrophosphate
  • Interferon-gamma