Stimulation of the specific immune system by mistletoe extracts

We have investigated the in vitro responsiveness of T cells from mistletoe-treated cancer patients and untreated donors to various preparations of mistletoe extracts. Proliferation of peripheral blood mononuclear cells from treated but not from untreated patients was observed in response to therapeutically used mistletoe extracts prepared from apple (mali) or pine (pini) host trees. The strongest proliferation was induced by vesicle preparation of mali extract. Using a newly developed flow cytometry assay (standard cell dilution assay), we determined that cell growth was restricted to CD4+ T cells. Analysis with a panel of monoclonal antibodies against variable regions of the T cell receptor beta chain (V beta) revealed an oligoclonal pattern of CD4+ T cell activation. These results indicate that therapeutic administration of mistletoe extracts sensitized a restricted set of CD4+ T lymphocytes in mistletoe-treated patients. Lymphocytes from untreated donors are only stimulated with heat-treated mistletoe extracts. The responding T cells are gamma delta T cells and express 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.