Ostankovitch M, Buzyn A, Bonhomme D, Connan F, Bouscary D, Heshmati F, Dreyfus F, Choppin J, Guillet J G
Institut Cochin de Génétique Moléculaire, INSERM U445, France.
Blood. 1998 Jul 1;92(1):19-24.
Recent studies have shown that transfusions of HLA-compatible donor lymphocytes may induce complete remission in marrow-grafted patients with relapses of acute myeloblastic leukemia (AML). We investigated the in vitro generation of antileukemia T-cell clones obtained from the peripheral blood mononuclear cells of a partially HLA-compatible donor (HLA-A2 and B7 molecules in common with the leukemic blasts) after stimulation with a pool of naturally processed peptides extracted from leukemic blast cells collected at diagnosis from a patient with hyperleucocytosis AML. We recovered a significant quantity of peptides that bound to the HLA-A2 or HLA-B7 molecules that were able to induce cytolytic T-lymphocyte (CTL) lines and clones specific for the eluted AML peptides and restricted to the HLA-A2 or B7 molecules. Such CTL line did not recognize the patient's nonleukemic cells, and one clone was able to interact with the leukemic blasts from which the naturally processed peptides had been eluted. Such T-cell clones might provide a rationale for the development of adoptive immunotherapy and could be used to improve the efficiency of HLA-compatible T-lymphocyte transfusions and the graft-versus-leukemia response in patients with AML.
最近的研究表明，输注HLA相容的供体淋巴细胞可能会使急性髓细胞白血病（AML）复发的骨髓移植患者实现完全缓解。我们研究了从一名部分HLA相容供体（与白血病母细胞共有HLA-A2和B7分子）的外周血单个核细胞中获得的抗白血病T细胞克隆在体外的生成情况，该供体的外周血单个核细胞在受到从一名高白细胞血症AML患者诊断时采集的白血病母细胞中提取的一组天然加工肽刺激后。我们回收了大量与HLA-A2或HLA-B7分子结合的肽，这些肽能够诱导针对洗脱的AML肽且受限于HLA-A2或B7分子的细胞毒性T淋巴细胞（CTL）系和克隆。这种CTL系不识别患者的非白血病细胞，并且一个克隆能够与洗脱天然加工肽的白血病母细胞相互作用。这种T细胞克隆可能为过继性免疫疗法的发展提供理论依据，并可用于提高HLA相容T淋巴细胞输注的效率以及AML患者的移植物抗白血病反应。
