Natural killer (NK)-cell function and antileukemic activity of a large population of CD3(+)/CD8(+) T cells expressing NK receptors for major histocompatibility complex class I after ''three-loci'' HLA-incompatible bone marrow transplantation
Natural killer (NK)-cell function and antileukemic activity of a large population of CD3(+)/CD8(+) T cells expressing NK receptors for major histocompatibility complex class I after ''three-loci'' HLA-incompatible bone marrow transplantation
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DOI：
10.1182/blood.v87.9.3993.bloodjournal8793993
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发表时间：
1996-05-01
期刊：
影响因子：
20.3
通讯作者：
Velardi, A
中科院分区：
文献类型：
--
作者：
Albi, N;Ruggeri, L;Velardi, A
我们已经证明，将粒细胞集落刺激因子动员的外周血祖细胞添加到骨髓接种物中，可以移植t细胞耗尽、“三位点”hla不相容的急性白血病骨髓移植。复发高风险患者的无事件生存促使目前对这种移植的抗肿瘤潜力进行研究。自然杀伤（NK）细胞的肿瘤细胞裂解受特定HLA I类等位基因的抑制受体调控。在这里，我们报告了移植后出现的大量供体型CD3(+)/CD8(+) t细胞受体(TcR)- α / β(+)细胞群，在正常受试者中几乎检测不到，表达58 kD，“p58”NK受体的HLA-C位点等位基因。对bbb900克隆的分析显示，这些T细胞中有40%至80%具有nk样功能，即它们裂解I类靶标，并被靶细胞上的I类等位基因功能性阻断。这些细胞通过单克隆抗体介导的I类识别阻断诱导hla保护的自体靶点裂解。通过NK受体介导的i类抑制信号也阻断了TcR/ cd3触发的这些细胞的细胞毒性，表明它们的抗原特异性反应可能受损。然而，这些细胞的nk样功能使它们能够区分正常细胞（不受裂解的保护）和被裂解的白血病细胞，并可能成为移植物抗白血病效应的靶点。(C) 1996年由美国血液病学会出版。
We have shown that addition of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to the marrow inoculum allows engraftment of T-cell depleted, ''three loci'' HLA-incompatible marrow transplants for acute leukemia. The event-free survival of patients at high risk for relapse prompted the present investigation of the antitumor potential of this transplant. Tumor-cell lysis by natural killer (NK) cells is regulated by inhibitory receptors for specific HLA class I alleles. Here, we report the postgrafting emergence of a large, donor-type CD3(+)/CD8(+) T-cell receptor (TcR)-alpha/beta(+) cell population, barely detectable in normal subjects, that expresses 58 kD, ''p58,'' NK receptors for HLA-C locus alleles. Analysis of >900 clones revealed that 40% to 80% of these T cells exhibit NK-like function, ie, they lysed class I- targets and were functionally blocked by class I alleles on target cells. Monoclonal antibody-mediated blocking of class I recognition by these cells induced lysis of HLA-protected, autologous targets. The class I-mediated inhibitory signaling through the NK receptors also blocked TcR/CD3-triggered cytotoxicity of these cells, indicating that their antigen-specific responses may be impaired. However, the NK-like function of these cells allows them to discriminate normal cells, protected from lysis, from leukemic cells that were lysed and may be targets for a graft-versus-leukemia effect. (C) 1996 by The American Society of Hematology.