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Activation of human gamma delta T-cells by heat-treated mistletoe plant extracts
S Fischer1, A Scheffler, D Kabelitz
1Department of Immunology, Paul Ehrlich Institute, Langen, Germany.
Abstract:
Various microorganisms including mycobacteria, other bacteria and parasites such as Plasmodium falciparum are known to activate human gamma delta T-cells in vitro. In this study, we demonstrate that heat-treated (but not untreated) mistletoe extracts similarly stimulate human gamma delta T-cells during in vitro culture. The responding T-cells express the variable T-cell receptor elements V gamma 9 and V delta 2. The gamma delta-stimulating activity of heat-treated mistletoe extracts is sensitive to treatment with alkaline phosphatase but not with proteinase K, indicating that the ligands are non-proteinaceous phosphate-containing compounds. Mistletoe-derived ligands share these features with the previously defined mycobacteria-derived ligands for gamma delta T-cells.
Insights
Heat-treated mistletoe extracts stimulate human gamma delta T-cells, similar to mycobacteria. The active compounds are non-proteinaceous and contain phosphate, activating V gamma 9 V delta 2 T-cells.
Area of Science:
- Immunology
- Microbiology
- Natural Products
Background:
- Human gamma delta T-cells are activated by various microorganisms like mycobacteria and parasites.
- These T-cells express specific T-cell receptor (TCR) elements, V gamma 9 and V delta 2.
- Understanding novel activators of gamma delta T-cells is crucial for immune modulation.
Purpose of the Study:
- To investigate the potential of mistletoe extracts to stimulate human gamma delta T-cells.
- To characterize the nature of the mistletoe-derived ligands responsible for T-cell activation.
- To compare mistletoe-derived ligands with known microbial ligands for gamma delta T-cells.
Main Methods:
- In vitro culture of human peripheral blood mononuclear cells (PBMCs).
- Stimulation assays using heat-treated and untreated mistletoe extracts.
- Flow cytometry to analyze T-cell receptor expression (V gamma 9, V delta 2).
- Enzymatic treatments (alkaline phosphatase, proteinase K) to characterize ligands.
Main Results:
- Heat-treated mistletoe extracts significantly stimulated human gamma delta T-cells expressing V gamma 9 V delta 2 TCRs.
- Untreated mistletoe extracts did not induce a similar T-cell response.
- The stimulating activity was abolished by alkaline phosphatase but not proteinase K treatment.
- This indicates the presence of non-proteinaceous, phosphate-containing compounds in mistletoe extracts.
Conclusions:
- Heat-treated mistletoe extracts contain ligands that activate human V gamma 9 V delta 2 gamma delta T-cells.
- These mistletoe-derived ligands are phosphate-containing, non-proteinaceous molecules.
- The identified ligands share characteristics with mycobacteria-derived ligands, suggesting conserved activation mechanisms for gamma delta T-cells.