TRAIL expression by activated human CD4(+)V alpha 24NKT cells induces in vitro and in vivo apoptosis of human acute myeloid leukemia cells.

Nieda, M; Nicol, A; Koezuka, Y; Kikuchi, A; Lapteva, N; Tanaka, Y; Tokunaga, K; Suzuki, K; Kayagaki, N; Yagita, H; Hirai, H; Juji, T

Nieda, M; Nicol, A; Koezuka, Y; Kikuchi, A; Lapteva, N; Tanaka, Y; Tokunaga, K; Suzuki, K; Kayagaki, N; Yagita, H; Hirai, H; Juji, T.

Afiliación

Nieda M; Department of Research of the Japanese Red Cross Central Blood Center; Japanase Red Cross Hospital, Tokyo, Japan. nieda@cbc.jrc.or.jp

Blood ; 97(7): 2067-74, 2001 Apr 01.

Article en En | MEDLINE | ID: mdl-11264173

RESUMEN

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)

Asunto(s)

Apoptosis/fisiología; Linfocitos T CD4-Positivos/metabolismo; Células Dendríticas/inmunología; Galactosilceramidas/farmacología; Inmunoterapia Adoptiva; Leucemia Mielomonocítica Aguda/patología; Glicoproteínas de Membrana/fisiología; Subgrupos de Linfocitos T/metabolismo; Factor de Necrosis Tumoral alfa/fisiología; Adulto; Animales; Anticuerpos Monoclonales/inmunología; Antígenos CD1/fisiología; Antígenos CD1d; Proteínas Reguladoras de la Apoptosis; Linfocitos T CD4-Positivos/clasificación; Linfocitos T CD4-Positivos/inmunología; Linfocitos T CD4-Positivos/trasplante; Células Cultivadas; Técnicas de Cocultivo; Femenino; Sangre Fetal/citología; Células Madre Hematopoyéticas/metabolismo; Humanos; Leucemia Mieloide/patología; Leucemia Mieloide Aguda/patología; Leucemia Mielomonocítica Aguda/inmunología; Leucemia Mielomonocítica Aguda/terapia; Activación de Linfocitos; Masculino; Glicoproteínas de Membrana/antagonistas & inhibidores; Glicoproteínas de Membrana/biosíntesis; Glicoproteínas de Membrana/inmunología; Ratones; Ratones Endogámicos NOD; Ratones SCID; Persona de Mediana Edad; Trasplante de Neoplasias; Células Madre Neoplásicas/metabolismo; Receptores de Antígenos de Linfocitos T/inmunología; Subgrupos de Linfocitos T/inmunología; Subgrupos de Linfocitos T/trasplante; Ligando Inductor de Apoptosis Relacionado con TNF; Factor de Necrosis Tumoral alfa/antagonistas & inhibidores; Factor de Necrosis Tumoral alfa/biosíntesis; Factor de Necrosis Tumoral alfa/inmunología; Ensayos Antitumor por Modelo de Xenoinjerto

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Glicoproteínas de Membrana / Leucemia Mielomonocítica Aguda / Linfocitos T CD4-Positivos / Inmunoterapia Adoptiva / Subgrupos de Linfocitos T / Factor de Necrosis Tumoral alfa / Apoptosis / Galactosilceramidas Tipo de estudio: Prognostic_studies Idioma: En Revista: Blood Año: 2001 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos

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