Bellantuono Ilaria, Gao Liquan, Parry Suzanne, Marley Steve, Dazzi Francesco, Apperley Jane, Goldman John M, Stauss Hans J
Department of Immunology, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom.
Blood. 2002 Nov 15;100(10):3835-7. doi: 10.1182/blood.V100.10.3835.
Using the allo-restricted T-cell approach to circumvent tolerance, we have previously identified a cytotoxic T-lymphocyte (CTL) epitope in the transcription factor Wilms tumor antigen 1 (WT1) presented by HLA-A0201 (A2) class I molecules. Here we describe an additional A2-presented epitope and show that CTLs against both epitopes kill WT1-expressing leukemia cell lines. Colony-forming assays demonstrated that both types of CTL killed CD34(+) progenitor cells from A2(+) leukemia patients, but not from A2(+) healthy individuals. The long-term culture-initiating cell (LTC-IC) assay was used to analyze the killing activity of WT1-specific CTLs against the more immature fraction of CD34(+) cells. The CTLs killed LTC-ICs of patients with chronic myelogenous leukemia (CML), whereas the function of normal CD34(+) progenitor/stem cells was not inhibited. Together, the data show that CTLs specific for 2 distinct peptide epitopes of WT1 can discriminate between normal and leukemia LTC-ICs, suggesting that such CTLs have the potential to selectively kill CML progenitor/stem cells.
利用同种异体限制性T细胞方法来规避免疫耐受，我们之前在由HLA - A0201（A2）I类分子呈递的转录因子威尔姆斯瘤抗原1（WT1）中鉴定出了一个细胞毒性T淋巴细胞（CTL）表位。在此我们描述了另一个由A2呈递的表位，并表明针对这两个表位的CTL均可杀伤表达WT1的白血病细胞系。集落形成试验表明，这两种类型的CTL均可杀伤来自A2(+)白血病患者的CD34(+)祖细胞，但不会杀伤来自A2(+)健康个体的CD34(+)祖细胞。长期培养起始细胞（LTC - IC）试验用于分析WT1特异性CTL对CD34(+)细胞中更不成熟部分的杀伤活性。这些CTL可杀伤慢性髓性白血病（CML）患者的LTC - IC，而正常CD34(+)祖细胞/干细胞的功能未受抑制。总之，数据表明针对WT1的2个不同肽表位的CTL可区分正常和白血病LTC - IC，这表明此类CTL有选择性杀伤CML祖细胞/干细胞的潜力。
