CD8+ minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells
CD8+ minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells
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DOI：
10.1073/pnas.96.15.8639
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发表时间：
1999-07-20
影响因子：
11.1
通讯作者：
Riddell, SR
中科院分区：
文献类型：
--
作者：
Bonnett, D;Warren, EH;Riddell, SR
基于T淋巴细胞输注的人类白血病的有效免疫疗法需要鉴定靶向白血病干细胞的效应T细胞。将人急性髓性白血病移植到非肥胖糖尿病/严重联合免疫缺陷（SCID）小鼠中，发现了一种罕见的白血病祖细胞，称为SCID白血病起始细胞，其在白血病人群中的频率较低，对建立白血病造血至关重要。因此，这种移植模型可能非常适合于鉴定具有抗白血病活性的效应T细胞。我们报道了特异于次要组织相容性抗原的CD 8（+）细胞毒性T淋巴细胞（CTL）克隆抑制非肥胖糖尿病/SCID小鼠中人急性髓系白血病细胞的植入，并证明这种抑制是通过直接CTL识别SCID白血病起始细胞介导的。这些结果表明，CD 8（+）次要组织相容性抗原特异性CTL可能是异基因造血细胞移植相关的移植物抗白血病效应的介质，并提供了一个实验模型，以识别和选择T细胞克隆免疫治疗，以预防或治疗异基因造血细胞移植后复发。
Effective immunotherapy for human leukemia based on infusions of T lymphocytes requires the identification of effector T cells that target the leukemic stem cell. The transplantation of human acute myeloid leukemia into nonobese diabetic/severe combined immune deficient (SCID) mice has identified a rare leukemic progenitor termed the SCID leukemia-initiating cell, which is present in low frequency in the leukemic population and is essential for establishing leukemic hematopoiesis. Thus, this transplant model may be ideally suited to identify effector T cells with antileukemic activity. We report that CD8(+) cytotoxic T lymphocyte (CTL) clones specific for minor histocompatibility antigens inhibit the engraftment of human acute myeloid leukemia cells in nonobese diabetic/SCID mice and demonstrate that this inhibition is mediated by direct CTL recognition of SCID leukemia-initiating cells. These results indicate that CD8(+) minor histocompatibility antigen-specific CTL may be mediators of the graft-versus-leukemia effect associated with allogeneic hematopoietic cell transplantation and provide an experimental model to identify and select T cell clones for immunotherapy to prevent or treat relapse after allogeneic hematopoietic cell transplantation.