GROWTH-INHIBITION OF CLONOGENIC LEUKEMIC PRECURSOR CELLS BY MINOR HISTOCOMPATIBILITY ANTIGEN-SPECIFIC CYTOTOXIC LYMPHOCYTES-T
GROWTH-INHIBITION OF CLONOGENIC LEUKEMIC PRECURSOR CELLS BY MINOR HISTOCOMPATIBILITY ANTIGEN-SPECIFIC CYTOTOXIC LYMPHOCYTES-T
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DOI：
10.1084/jem.174.1.27
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发表时间：
1991-07-01
影响因子：
15.3
通讯作者：
GOULMY, E
中科院分区：
文献类型：
--
作者：
FALKENBURG, JHF;GOSELINK, HM;GOULMY, E
次要组织相容性 (mH) 抗原似乎在使用 HLA 相同供体的骨髓移植 (BMT) 中发挥着重要作用。此前，我们报道了从患有移植物抗宿主病或 HLA 一致 BMT 后排斥反应的患者中分离出主要组织相容性复合物 (MHC) 限制性 mH 抗原特异性细胞毒性 T 淋巴细胞 (CTL)。我们已经证明，mH 抗原可以在造血祖细胞上被识别，并且尽管在 HLA 相同的 BMT 中采用强化调理方案，但对供体造血祖细胞上表达的 mH 抗原具有特异性的残留受体 CTL 可能导致移植排斥。在这里，我们研究了针对 mH 抗原 HA-1 至 HA-5 和男性特异性抗原 H-Y 的 mH 抗原特异性 CTL 是否能够抗原特异性抑制克隆性白血病前体细胞的体外生长。我们证明，针对所有测试的 mH 抗原的 mH 抗原特异性 CTL 可以裂解新鲜获得的髓系白血病细胞，这些 mH 抗原特异性 CTL 可以在体外抑制其克隆性白血病生长，并且这种识别受到 MHC 限制。我们说明白血病（前体）细胞可以通过相关 MHC 限制分子的表达受损来逃避 mH 抗原特异性 CTL 的消除。我们认为，mH 抗原特异性 MHC 限制性 CTL 可能在体内参与 BMT 后的移植物抗白血病反应。
Minor histocompatibility (mH) antigens appear to play a major role in bone marrow transplantation (BMT) using HLA-identical donors. Previously, we reported the isolation of major histocompatibility complex (MHC)-restricted mH antigen-specific cytotoxic T lymphocytes (CTL) from patients with graft-vs.-host disease or rejection after HLA-identical BMT. We have demonstrated that mH antigens can be recognized on hematopoietic progenitor cells, and residual recipient CTL specific for mH antigens expressed on donor hematopoietic progenitor cells may be responsible for graft rejection in spite of intensive conditioning regimens in HLA-identical BMT. Here, we investigated whether mH antigen-specific CTL directed against the mH antigens HA-1 to HA-5 and the male-specific antigen H-Y were capable of antigen-specific inhibition of in vitro growth of clonogenic leukemic precursor cells. We demonstrate that mH antigen-specific CTL against all mH antigens tested can lyse freshly obtained myeloid leukemic cells, that these mH antigen-specific CTL can inhibit their clonogenic leukemic growth in vitro, and that this recognition is MHC restricted. We illustrate that leukemic (precursor) cells can escape elimination by mH antigen-specific CTL by impaired expression of the relevant MHC restriction molecule. We suggest that mH antigen-specific MHC-restricted CTL may be involved in vivo in the graft-vs.-leukemia reactivity after BMT.