Reduced Expression of the Mevalonate Pathway Enzyme Farnesyl Pyrophosphate Synthase Unveils Recognition of Tumor Cells by V gamma 9V delta 2 T Cells
Jianqiang Li, Marco J Herold, Brigitte Kimmel, Ingrid Mueller, Bladimiro Rincon-Orozco, Volker Kunzmann, Thomas Herrmann
The Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2009
Human Vgamma9Vdelta2 T cells are characterized by a unique specificity for certain tumors (e.g., Daudi), cells presenting so-called phosphoantigens such as isopentenyl pyrophosphate (IPP), or cells treated with aminobisphosphonates. We now report conversion of hematopoietic and nonhematopoietic tumor cell lines into Vgamma9Vdelta2 T cell activators by means of short hairpin RNA-mediated knockdown of expression of the IPP-consuming enzyme, farnesyl pyrophosphate synthase (FPPS). FPPS knockdown cells activated Vgamma9Vdelta2 T cells, as measured by increased levels of CD69 and CD107a, killing of FPPS knockdown cells, and induction of IFN-gamma secretion. The IPP-synthesis-inhibiting drug mevas..View full abstract
Awarded by Interdiziplinares Zentrum fur Klinische Forschung
This work was supported by Interdiziplinares Zentrum fur Klinische Forschung Grant No. 01KS9603.