The antileukemia effect of HLA-matched NK and NK-T cells in chronic myelogenous leukemia involves NKG2D-target-cell interactions
The antileukemia effect of HLA-matched NK and NK-T cells in chronic myelogenous leukemia involves NKG2D-target-cell interactions
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DOI：
10.1182/blood-2005-02-0479
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发表时间：
2005-11-15
期刊：
影响因子：
20.3
通讯作者：
Barrett, AJ
中科院分区：
文献类型：
--
作者：
Sconocchia, G;Lau, M;Barrett, AJ
为研究自然杀伤（NK）细胞对慢性粒细胞白血病（CIVIL）的抗白血病作用，我们研究了HLA相合和不相合的CD 56（+）细胞对白血病CD 34（+）细胞形成粒细胞-巨噬细胞集落形成单位（CFU-GM）的抑制作用。在14对HLA相同的供体-受体中，供体CD 56（+）细胞抑制了来自14个HLA不匹配的无关个体的CIVIL CFU-GM对效应子的增殖（在10：1的效应子-靶（E/T）比下，平均抑制率为42% +/- 9% vs 39.5% +/- 7%），表明杀伤抑制受体（KIR）不相容性对于抗白血病作用不是必需的。CD 56（+）CD 3（-）（NK）和CD 56（+）CD 3（+）（NK-T）细胞均能抑制CML的CFU-GM生长，但对正常CD 34（+）细胞无抑制作用。CIVIL CD 34细胞上主要组织相容性I类链相关基因A或基因B（云母/B）的异常过表达及其结合NK活化配体NKG 2D的能力提示了这种白血病特异性细胞毒性的机制。然而，在体内，CIVIL细胞可以通过免疫逃逸避免NK细胞介导的免疫破坏，将云母脱落到血浆中，从而下调CIVIL CD 56（+）细胞上的NKG 2D。
To study natural killer (NK) cell-mediated antileukemic activity in chronic myelogenous leukemia (CIVIL), we investigated the ability of HLA-matched and mismatched CD56(+) cells to inhibit granulocyte macrophage-colony-forming unit (CFU-GM) formation by leukemic CD34(+) cells. In 14 HLA-identical donor-recipient pairs, donor CD56(+) cells inhibited CIVIL CFU-GM comparably to effectors from 14 HLA-mismatched unrelated individuals (mean inhibition 42% +/- 9% vs 39.5% +/- 7% at a 10:1 effector-to-target (E/T) ratio), suggesting that killer inhibitory receptor (KIR) incompatibility was not essential for an antileukemic effect. Both CD56(+)CD3(-) (natural killer [NK]) and CD56(+)CD3(+)(NK-T) cells inhibited CFU-GM growth of CML but not normal CD34(+) cells. A mechanism for this leukemia-specific cytotoxicity was suggested by the abnormal overexpression of major histocompatibility class I chain-related gene A or gene B (MICA/B) on CIVIL CD34 cells and their ability to bind the NK activation ligand NKG2D. However, in vivo, CIVIL cells may avoid NK-cell-mediated immune destruction by immune escape, shedding MICA into the plasma, thereby down-regulating NKG2D on CIVIL CD56(+) cells.