RESUMEN
The Wilms tumor (WT1) gene has been reported to be preferentially expressed in acute leukemia cells, regardless of leukemia subtype and chronic myelogenous leukemia cells in blast crisis, but not in normal cells. This finding suggests strongly that WT1 protein is a potential target of immunotherapy for human leukemia. In this study, we established a CD8(+) cytotoxic T-lymphocyte (CTL) clone directed against a WT1-derived peptide and examined its immunologic actions on leukemia cells. A CD8(+) CTL clone, designated TAK-1, which lysed autologous cells loaded with a WT1-derived 9-mer peptide consisting of the HLA-A24 (HLA-A*2402)-binding motifs was established by stimulating CD8(+) T lymphocytes from a healthy individual repeatedly with WT1 peptide-pulsed autologous dendritic cells. TAK-1 was cytotoxic to HLA-A24-positive leukemia cells expressing WT1, but not to HLA-A24-positive lymphoma cells that did not express WT1, HLA-A24-negative leukemia cells, or HLA-A24-positive normal cells. Treating leukemia cells with an antisense oligonucleotide complementary to the WT1 gene resulted in reduced TAK-1-mediated cytotoxicity, suggesting that target antigen of TAK-1 on leukemia cells is the naturally processed WT1 peptide in the context of HLA-A24. TAK-1 did not inhibit colony formation by normal bone marrow cells of HLA-A24-positive individuals. Because WT1 is overexpressed ubiquitously in various types of leukemia cells, but not in normal cells, immunotherapy using WT1 peptide-specific CTL clones should be an efficacious treatment for human leukemia. (Blood. 2000;95:286-293)
Asunto(s)
Linfocitos B/inmunología , Células de la Médula Ósea/inmunología , Citotoxicidad Inmunológica , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/inmunología , Antígenos HLA-A/inmunología , Leucemia/inmunología , Linfoma/inmunología , Oligodesoxirribonucleótidos Antisentido/farmacología , Linfocitos T Citotóxicos/inmunología , Factores de Transcripción/genética , Factores de Transcripción/inmunología , Secuencia de Aminoácidos , Secuencia de Bases , Células de la Médula Ósea/citología , Línea Celular Transformada , Células Cultivadas , Células Clonales , Ensayo de Unidades Formadoras de Colonias , Exones , Antígenos HLA-A/genética , Antígeno HLA-A24 , Herpesvirus Humano 4 , Humanos , Japón , Datos de Secuencia Molecular , Fragmentos de Péptidos/inmunología , Células Tumorales Cultivadas , Proteínas WT1 , Dedos de ZincRESUMEN
We examined the effects of oyster (Ostrea gingas Thunb.) water extracts on hyperlipemia and liver injury produced in rats by feeding on peroxidized oil. The extracts of oyster were found to reduce the levels of serum free fatty acid, triglyceride, lipid peroxide and liver cholesterol in the peroxidized oil-treated rats. In addition, we found that the water extracts of oyster inhibited adrenaline-induced lipolysis, and that these extracts stimulated lipogenesis from glucose in isolated fat cells of rats. The active substance was isolated and identified as adenosine by direct comparison with an authentic sample.