Expression of human leucocyte antigens and co-stimulatory molecules on blasts of patients with acute myeloid leukaemia
Expression of human leucocyte antigens and co-stimulatory molecules on blasts of patients with acute myeloid leukaemia
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DOI：
10.1046/j.1365-2141.2003.04212.x
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发表时间：
2003-03-01
影响因子：
6.5
通讯作者：
Schmitt, M
中科院分区：
文献类型：
--
作者：
Vollmer, M;Li, L;Schmitt, M
最近，T淋巴细胞识别的白血病相关抗原（LAA），如Wilm肿瘤-1（WT-1）或发病相关蛋白-1（PR-1）已被鉴定。对于采用抗原肽的免疫疗法，无论是单独的还是在树突状细胞（DC）上脉冲的，人白细胞抗原（HLA）分子在靶向白血病母细胞（LB）上的表达是至关重要的。共刺激分子CD 80和CD 86向T淋巴细胞提供溶解白血病细胞所必需的次级信号，并且CD 40增强抗原呈递的功效。在这里，HLA-ABC，HLA-A2，HLA-DR，CD 40，CD 80和CD 86的表达进行了流式细胞术检测血液样品中24名健康志愿者（HV），24例新诊断的急性髓性白血病（AML）和5例复发AML患者。与HV单核细胞相比，LB细胞表面HLA-ABC、CD 40、CD 80和CD 86的表达明显降低。HLA-A2和HLA-DR在LB和HV单核细胞上的表达相似。在AML患者中，LB上的HLA和CD 86分子的表达显著高于CD 33/CD 34阴性单核细胞。AML母细胞上CD 40和CD 80分子缺乏。大多数AML患者在诊断时甚至在疾病复发时LB上的HLA分子和CD 86的保留是这些患者中LAA靶向免疫治疗的先决条件。
Recently, leukaemia-associated antigens (LAA) recognized by T lymphocytes, such as Wilm's tumour-1 (WT-1) or pathogenesis-related protein-1 (PR-1), have been identified. For immunotherapies that employ antigen peptides, either alone or pulsed on dendritic cells (DC), the expression of human leucocyte antigen (HLA) molecules on the targeted leukaemic blasts (LB) is crucial. The co-stimulatory molecules CD80 and CD86 give the secondary signal to T lymphocytes that is necessary for the lysis of leukaemia cells, and CD40 enhances the efficacy of antigen presentation. Here, the expression of HLA-ABC, HLA-A2, HLA-DR, CD40, CD80 and CD86 was flow cytometrically examined in blood samples from 24 healthy volunteers (HV), 24 patients with newly diagnosed acute myeloid leukaemia (AML) and five patients with relapsed AML. The expression of HLA-ABC, CD40, CD80 and CD86 was significantly reduced on LB in comparison with monocytes of HV. HLA-A2 and HLA-DR expression was similar on LB and on monocytes of HV. In AML patients, the expression of HLA and CD86 molecules was significantly higher on LB than on CD33/CD34-negative monocytes. CD40 and CD80 molecules were deficient on AML blasts. The preservation of HLA molecules and CD86 on LB of the majority of AML patients at the time of diagnosis and even at relapse of the disease are prerequisites for LAA-targeted immunotherapies in these patients.