In vivo manipulation of γ9(+) T cells in the common marmoset (Callithrix Jacchus) with phosphoantigen and effect on the progression of respiratory melioidosis

PLoS One. 2013 Sep 30;8(9):e74789. doi: 10.1371/journal.pone.0074789. eCollection 2013.

Abstract

Burkholderia pseudomallei is a dangerous human pathogen. Phosphoantigens specifically the target primate specific γ9(+)δ2(+) T cells subset and some have been developed as potential immunotherapeutics. Previously, we demonstrated that, when stimulated with the phosphoantigen CHDMAPP, γ9(+)δ2(+) T cells aid in the killing of intracellular B. pseudomallei bacteria. Moreover, we found that common marmoset (Callithrix Jacchus) γ9(+) T cells increase in frequency and respond to the phosphoantigen CHDMAPP and/or B. pseudomallei, in combination with IL-2, in a similar manner to human γ9(+)δ2(+) T cells. Here we evaluate the efficacy of the phosphoantigen CHDMAPP, in combination with IL-2, as a therapy against B. pseudomallei infection, in vivo. We found that the previous studies predicted the in vivo responsiveness of γ9(+) T cells to the CHDMAPP+IL-2 treatment and significant expansion of the numbers of peripheral and splenic γ9(+) T cells were observed. This effect was similar to those reported in other primate species treated with phosphoantigen. Furthermore, splenocytes were retrieved 7 days post onset of treatment, restimulated with CHDMAPP or heat-killed B. pseudomallei and the cultured γ9(+) T cells demonstrated no reduction in IFN-γ response when CHDMAPP+IL-2 animals were compared to IL-2 only treated animals. Using an established model of B. pseudomallei infection in the marmoset, we assessed the potential for using phosphoantigen as a novel immunotherapy. The CHDMAPP treatment regime had no effect on the progression of respiratory melioidosis and this was despite the presence of elevated numbers of γ9(+) T cells in the spleen, liver and lung and an increased proportion of IFN-γ(+) cells in response to infection. We therefore report that the common marmoset has proven a good model for studying the effect in vivo of γ9(+) T cell stimulation; however, γ9(+) T cells have little or no effect on the progression of lethal, respiratory B. pseudomallei infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Burkholderia pseudomallei / immunology*
  • Callithrix*
  • Flow Cytometry
  • Immunotherapy / methods*
  • Interferon-gamma / metabolism
  • Interleukin-2 / immunology
  • Melioidosis / drug therapy
  • Melioidosis / immunology
  • Melioidosis / veterinary*
  • Monkey Diseases / drug therapy*
  • Monkey Diseases / immunology*
  • Phosphoproteins / immunology
  • Phosphoproteins / pharmacology
  • Phosphoproteins / therapeutic use
  • T-Lymphocytes / metabolism*

Substances

  • Interleukin-2
  • Phosphoproteins
  • Interferon-gamma

Grants and funding

This work was funded by the British Ministry of Defence. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.