Nieda M, Nicol A, Koezuka Y, Kikuchi A, Lapteva N, Tanaka Y, Tokunaga K, Suzuki K, Kayagaki N, Yagita H, Hirai H, Juji T
Department of Research of the Japanese Red Cross Central Blood Center; Japanase Red Cross Hospital, Tokyo, Japan.
Blood. 2001 Apr 1;97(7):2067-74. doi: 10.1182/blood.v97.7.2067.
Human Valpha24NKT cells are activated by alpha-galactosylceramide (alpha-GalCer)-pulsed dendritic cells in a CD1d-dependent and a T-cell receptor-mediated manner. Here, we demonstrate that CD4(+)V alpha 24NKT 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 alpha-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 V alpha 24NKT 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 V alpha 24NKT 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(+)V alpha 24NKT cells induced apoptosis of human leukemia cells in vivo. This is the first evidence that activated V alpha 24NKT 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 V alpha 24NKT cells, or other strategies to increase activated V alpha 24NKT cells in vivo, may be of benefit to patients with AML M4. (Blood. 2001;97:2067-2074)
人Vα24 NKT细胞被α-半乳糖神经酰胺（α-GalCer）脉冲树突状细胞以CD1d依赖和T细胞受体介导的方式激活。在此，我们证明，来自急性髓系白血病（AML）M4患者的CD4(+)Vα24 NKT细胞在表型上与健康供体的细胞相似，并且与来自健康供体的细胞一样，当细胞被α-GalCer脉冲树突状细胞激活时表达肿瘤坏死因子相关凋亡诱导配体（TRAIL），但在激活之前不表达。我们还表明，AML M4患者的髓系白血病细胞，而不是AML M0或M1患者的细胞，在用表达TRAIL的自体或同种异体健康供体Vα24 NKT细胞培养后会发生凋亡。来自患者外周血的AML M4白血病细胞的凋亡几乎完全被抗TRAIL的中和单克隆抗体阻断，这表明Vα24 NKT细胞上的TRAIL对于诱导AML M4白血病细胞凋亡至关重要。非肥胖糖尿病-严重联合免疫缺陷人白血病（AML M4）模型显示，人活化的CD4(+)Vα24 NKT细胞在体内诱导人白血病细胞凋亡。这是第一个证据，表明活化的Vα24 NKT细胞表达TRAIL，并且TRAIL在体外和体内导致AML M4患者的单核细胞白血病细胞凋亡。用活化的Vα24 NKT细胞进行过继性免疫治疗，或其他在体内增加活化的Vα24 NKT细胞的策略，可能对AML M4患者有益。（《血液》。2001年；97:2067 - 2074）
