Synthetic phosphoantigens enhance human Vgamma9Vdelta2 T lymphocytes killing of non-Hodgkin's B lymphoma

Mol Med. 2001 Oct;7(10):711-22.


Background: Non-Hodgkin's B lymphomas (NHL) are often resistant to conventional treatments and, until now, immunotherapeutic approaches against NHL only aimed at inducing anti-tumor effectors. Nevertheless, human blood Vgamma9Vdelta2 T lymphocytes represent an abundant pool of cytotoxic tumor-reactive cells. Vgamma9Vdelta2 T cells are strongly activated by natural compounds, from which powerful synthetic ligands have been derived. These synthetic antigens induce efficient Vgamma9Vdelta2 T cell responses in vitro.

Materials and methods: We set up a series of Vgamma9Vdelta2 T cell-activation experiments, including cytotoxic activity and amplification from whole blood cells. Several types of Vgamma9Vdelta2 effectors were challenged against a panel of 16 B lymphoma cell lines. These tests have been performed in the absence and presence of -specific synthetic ligands to evaluate the effect of such molecules on anti-tumor activity.

Results: We report here that Vgamma9Vdelta2 T cells recognize B lymphomas. This recognition is associated with the cytotoxic activity against B-lymphoma cells and/or proliferative responses, and appears to be T-cell antigen receptor (TCR)-dependent. Because few B lymphoma induce a complete set of Vgamma9Vdelta2 cell responses, a chemical ligand of Vgamma9Vdelta2 T cells was used to enhance both proliferation and cytotoxic activity of anti-B lymphoma effectors. We show that such synthetic compound improves Vgamma9Vdelta2 CTL numbers and lysis of B lymphoma lines, especially when the targets are already spontaneously recognized by these effectors.

Conclusions: We report here that human Vgamma9Vdelta2 T cells anti-B lymphoma response can be improved by use of specific synthetic ligands, which enhance their cytotoxic activity and allows their rapid expansion ex vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Cytotoxicity, Immunologic / drug effects
  • Flow Cytometry
  • Humans
  • Lectins, C-Type
  • Ligands
  • Lymphocyte Activation / drug effects
  • Lymphoma, B-Cell / pathology*
  • Phosphoproteins / pharmacology*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Lectins, C-Type
  • Ligands
  • Phosphoproteins
  • Receptors, Antigen, T-Cell, gamma-delta