Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 59, Issue 7, Pages 1109-1120Publisher
SPRINGER
DOI: 10.1007/s00262-010-0839-8
Keywords
V gamma 9V delta 2 T cells; Dendritic cells; Human; Immunotherapy; Cytokines
Categories
Funding
- Engineering and Technology
- Science Foundation Ireland
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V gamma 9V delta 2 T cells respond to pyrophosphate antigens and display potent antitumour activity in vitro. We have investigated the potential of the most potent phosphoantigen known to activate V gamma 9V delta 2 T cells, (E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate (HMB-PP), as an adjuvant for dendritic cell (DC)-based vaccines. A single stimulation of peripheral blood mononuclear cells with HMB-PP and IL-2 was sufficient to generate lines of effector memory V gamma 9V delta 2 T cells that retained their cytolytic and cytokine secretion activities. These cells induced differentiation of DC into semi-mature antigen-presenting cells expressing CD86, CD11c, CD54, HLA-DR, CD83 and CD40, which secreted low levels of bioactive IL-12 but no IL-10. V gamma 9V delta 2 T cells also strongly costimulated IL-12 release but inhibited IL-10 production by lipopolysaccharide (LPS)-stimulated DC. When substituted for V gamma 9V delta 2 T cells, IFN-gamma did not induce full DC maturation but it augmented IL-12 and inhibited IL-10 release by LPS-stimulated DC, in a manner similar to HMB-PP-activated V gamma 9V delta 2 T cells. Our findings indicate that V gamma 9V delta 2 T cells, stimulated with nanomolar concentrations of HMB-PP, strongly promote T helper type 1 (Th1) responses through their ability to induce DC maturation and IL-12 secretion. This adjuvant activity may prove useful in DC-based cancer therapies.
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