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恒河猴经抗T淋巴细胞单克隆抗体预处理后骨髓移植的再增殖能力。

The repopulation capacity of bone marrow grafts following pretreatment with monoclonal antibodies against T lymphocytes in rhesus monkeys.

作者信息

Gerritsen W R, Wagemaker G, Jonker M, Kenter M J, Wielenga J J, Hale G, Waldmann H, van Bekkum D W

机构信息

Radiobiological Institute TNO, Rijswijk, The Netherlands.

出版信息

Transplantation. 1988 Feb;45(2):301-7. doi: 10.1097/00007890-198802000-00010.

Abstract

Complement-mediated lysis of (subsets of) T lymphocytes in bone marrow grafts is increasingly used to prevent acute graft-versus-host disease in human bone marrow transplant recipients, especially in case of major immunogenetic disparity between donor and recipient. Since T lymphocyte depletion has resulted in an increased frequency of allogeneic engraftment failures, its effect on hemopoietic reconstitution was measured in rhesus monkeys. The reactivity patterns of commonly used types of antihuman T lymphocyte monoclonal antibodies (MCAs) with rhesus monkey lymphocytes was analyzed using a double-label cytofluorometry technique and found to be very similar to those with human lymphocytes. The antibodies investigated included CAMPATH-1 (recognizing an antigen present on virtually all lymphocytes and monocytes), OKT4 + 4a (CD4, helper/inducer T lymphocytes), B9 (CD8, suppressor/cytotoxic T lymphocytes), WT-1 (CD7, pan-T), and anti-DR MCAs as stem cell toxic controls. Their possible toxicity to hemopoietic stem cells was studied by using a semiquantitative autologous regeneration assay. Cytotoxic lysis of cells in the bone marrow grafts reacting with the T lymphocyte purging MCAs did not result in delayed regeneration compared to untreated autologous grafts. It is concluded that T lymphocyte depletion using anti-T-lymphocyte MCAs does not influence the repopulating capacity of an autologous bone marrow graft.

摘要

补体介导的骨髓移植中(部分)T淋巴细胞溶解越来越多地用于预防人类骨髓移植受者的急性移植物抗宿主病,尤其是在供体和受体之间存在主要免疫遗传差异的情况下。由于T淋巴细胞清除导致同种异体植入失败的频率增加,因此在恒河猴中测量了其对造血重建的影响。使用双标记细胞荧光测定技术分析了常用类型的抗人T淋巴细胞单克隆抗体(MCA)与恒河猴淋巴细胞的反应模式,发现与它们与人淋巴细胞的反应模式非常相似。所研究的抗体包括CAMPATH-1(识别几乎所有淋巴细胞和单核细胞上存在的一种抗原)、OKT4 + 4a(CD4,辅助/诱导性T淋巴细胞)、B9(CD8,抑制/细胞毒性T淋巴细胞)、WT-1(CD7,全T细胞)以及作为干细胞毒性对照的抗DR MCA。通过使用半定量自体再生试验研究了它们对造血干细胞的可能毒性。与未处理的自体移植物相比,与T淋巴细胞清除MCA反应的骨髓移植物中的细胞毒性溶解并未导致再生延迟。结论是,使用抗T淋巴细胞MCA清除T淋巴细胞不会影响自体骨髓移植物的再填充能力。

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