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白血病患者接受去除T细胞的人类白细胞抗原相同骨髓移植后的移植物失败:II. 宿主效应机制的体外分析

Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: II. In vitro analyses of host effector mechanisms.

作者信息

Bordignon C, Keever C A, Small T N, Flomenberg N, Dupont B, O'Reilly R J, Kernan N A

机构信息

Charles A. Dana Marrow Transplant Unit, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

出版信息

Blood. 1989 Nov 1;74(6):2237-43.

PMID:2529927
Abstract

To identify mechanisms potentially contributing to graft failure, 19 leukemic recipients of T-cell-depleted marrow transplants who failed to engraft following a transplant of HLA identical sibling marrow depleted of T cells by soybean agglutinin (SBA) and sheep erythrocytes (E) were evaluated. Peripheral blood mononuclear cells isolated at the time of failure were consistently of host origin, bearing the phenotype of suppressor T cells (CD3+, CD8+, Leu 7+). A direct cytolytic effect on 51Cr-labeled donor-derived target cells was not detected, a finding that contrasts with the donor-specific cytotoxic host T lymphocytes that have been regularly observed in patients rejecting HLA nonidentical SBA -E- BMTs. However, these host T cells did exhibit a strong and specific suppressive activity against the donor marrow CFU-GM in vitro. Furthermore, in contrast to prior findings in durably engrafted recipients of SBA -E- BMTs, the lymphocytes isolated prior to or at the time of graft failure lacked natural killer surface antigen expression and effector function.

摘要

为了确定可能导致移植失败的机制,我们对19例接受了大豆凝集素(SBA)和绵羊红细胞(E)去除T细胞的 HLA 同基因同胞骨髓移植但未成功植入的白血病患者进行了评估。移植失败时分离的外周血单个核细胞始终来源于宿主,具有抑制性T细胞的表型(CD3 +、CD8 +、Leu 7 +)。未检测到对51Cr标记的供体来源靶细胞的直接细胞溶解作用,这一发现与在排斥 HLA 非同基因 SBA -E-骨髓移植(BMT)的患者中经常观察到的供体特异性细胞毒性宿主T淋巴细胞形成对比。然而,这些宿主T细胞在体外确实对供体骨髓CFU-GM表现出强烈且特异性的抑制活性。此外,与之前在SBA -E- BMT持久植入受者中的发现相反,移植失败前或移植失败时分离的淋巴细胞缺乏自然杀伤表面抗原表达和效应功能。

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