Stimulation of Vgamma9/Vdelta2 T-lymphocyte proliferation by the isoprenoid precursor, (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate |
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Authors: | Amslinger Sabine Hecht Stefan Rohdich Felix Eisenreich Wolfgang Adam Petra Bacher Adelbert Bauer Stefan |
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Affiliation: | Lehrstuhl für Organische Chemie und Biochemie, Technische Universit?t München, Lichtenbergstr. 4, 85747 Garching, Germany. sabine.amslinger@chemie.uni-regensburg.de |
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Abstract: | (E)-1-Hydroxy-2-methyl-but-2-enyl 4-diphosphate, a recently discovered intermediate in the deoxyxylulose phosphate pathway of isoprenoid biosynthesis, has been shown to act as a potent immunomodulator. In cultures of human peripheral blood mononuclear cells from eight non-related donors, the compound stimulated the proliferation of Vgamma9/Vdelta2 T lymphocytes with a median EC(50) of 70 pM when 10 U/ml of IL-2 was used as costimulant. Isopentenyl diphosphate (IPP), dimethylallyl diphosphate (DMAPP) and some structural analogs of (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate also stimulated Vgamma9/Vdelta2 T-cell proliferation, albeit at much higher concentrations. The Vgamma9/Vdelta2 T-cell proliferation is highly dependent on the seeding density used in culture. All phosphoantigens tested elicited the proliferation of two T-lymphocyte populations with different apparent ratios between the expression level of Vdelta2 and Vgamma9 chains. |
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Keywords: | Deoxyxylulose phosphate γ δ T-cell activation 1-Hydroxy-2-methyl-but-2-enyl 4-diphosphate Isoprenoid biosynthesis |
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