Induction of Fas ligand (CD95L) by the toxic mistletoe lectins in human lymphocytes.

BACKGROUND

Fas ligand (FasL, CD95L) predominantly expressed on activated cytotoxic T cells and NK cells triggers apoptosis in Fas receptor (Apo-1, CD95) positive target cells. We investigated the expression of FasL, Fas and tumor necrosis factor (TNF) receptor 1 (TNF-R1, CD120a) on cultured human lymphocytes and leukemic T and B cells.

MATERIALS AND METHODS

Lymphocytes from six healthy individuals, from four patients with chronic lymphocytic T or B cell leukaemia, and leukemic Molt-4 cells were incubated with the apoptosis- inducing mistletoe lectins (ML I and ML III).

RESULTS

Incubation of differentiated lymphocytes with the ML resulted in a significant upregulation of FasL in the surviving CD4+ T helper cells, CD8+ cells and CD19+ B cells. Similarly, the TNF receptor expression increased, while the Fas molecule decreased. In contrast, FasL was not induced in leukemic cells.

CONCLUSIONS

Apart from a direct induction of apoptosis in response to an inhibition of protein synthesis by the enzymic ML A chain, ML treatment may indirectly induce apoptosis in Fas+ tumour cells through activated FasL+ lymphocytes.