TRAIL expression by activated human CD4+Valpha24NKT cells induces in vitro and in vivo apoptosis of human acute myeloid leukemia cells

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Abstract
Human Vα24NKT cells are activated by α-galactosylceramide (α-GalCer)-pulsed dendritic cells in a CD1d-dependent and a T-cell receptor–mediated manner. Here, we demonstrate that CD4+Vα24NKT cells derived from a patient with acute myeloid leukemia (AML) M4 are phenotypically similar to those of healthy donors and, in common with those derived from healthy donors, express tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) when the cells are activated by α-GalCer–pulsed dendritic cells but not prior to activation. We also show that myeloid leukemia cells from patients with AML M4, but not from patients with AML M0 or M1, undergo apoptosis following culture with TRAIL-expressing autologous or allogeneic healthy donor Vα24NKT cells. Apoptosis of AML M4 leukemia cells from patient peripheral blood was almost completely blocked by a neutralizing monoclonal antibody against TRAIL, indicating that TRAIL on Vα24NKT cells is essential for the induction of apoptosis in AML M4 leukemia cells. A nonobese diabetic–severe combined immunodeficient human leukemia (AML M4) model showed that human activated CD4+Vα24NKT cells induced apoptosis of human leukemia cells in vivo. This is the first evidence that activated Vα24NKT cells express TRAIL and that TRAIL causes apoptosis of monocytic leukemia cells from patients with AML M4 in vitro and in vivo. Adoptive immune therapy with activated Vα24NKT cells, or other strategies to increase activated Vα24NKT cells in vivo, may be of benefit to patients with AML M4.