Yoshino H, Ueda T, Kawahata M, Kobayashi K, Ebihara Y, Manabe A, Tanaka R, Ito M, Asano S, Nakahata T, Tsuji K
Department of Clinical Oncology, The Institute of Medical Science, The University of Tokyo, Japan.
Bone Marrow Transplant. 2000 Dec;26(11):1211-6. doi: 10.1038/sj.bmt.1702702.
The scid mutation was backcrossed on to the NOD/Shi mouse background, resulting in the development of NOD/Shi-scid mice, which showed lack of mature lymphocytes, macrophage dysfunction and absence of circulating complement, but were not as impaired in natural killer (NK) cell activity as NOD/LtSz-scid mice. We then examined the effect of recipient NK cell depletion by anti-asialo GM1 antiserum on the repopulation of human cord blood (CB) hematopoietic stem cells (HSC) in NOD/Shi-scid mice to clarify the role of recipient NK cells in human HSC engraftment. The anti-asialo GM1 antiserum treatment significantly enhanced the engraftment of CB CD34+ cells, but did not affect the differentiation of the engrafted HSC into each hematopoietic lineage. The NK cell depletion was effective at early stages of the engraftment, but not 3 weeks after the transplantation. The anti-asialo GM1 antiserum treatment did not improve the engraftment by human HSC in scid mice which lack mature lymphocytes, but show neither macrophage dysfunction nor a reduction in circulating complement, indicating that macrophages and/or complement also have roles in HSC graft rejection. The present study indicates that the preconditioning targeting of recipient NK cells in addition to T cell suppression and myeloablation might prevent HSC graft failure, and that NOD/Shi-scid mice treated with anti-asialo GM1 antiserum could provide a useful tool for evaluating the repopulating ability of transplantable human HSC.
将scid突变回交至NOD/Shi小鼠背景，培育出了NOD/Shi - scid小鼠，这些小鼠表现出成熟淋巴细胞缺乏、巨噬细胞功能障碍以及循环补体缺失，但在自然杀伤（NK）细胞活性方面不像NOD/LtSz - scid小鼠那样受损。然后，我们通过抗去唾液酸GM1抗血清耗尽受体NK细胞，来研究其对NOD/Shi - scid小鼠中人脐血（CB）造血干细胞（HSC）再增殖的影响，以阐明受体NK细胞在人HSC植入中的作用。抗去唾液酸GM1抗血清处理显著增强了CB CD34 +细胞的植入，但不影响植入的HSC向各造血谱系的分化。NK细胞耗竭在植入早期有效，但在移植后3周无效。抗去唾液酸GM1抗血清处理并不能改善缺乏成熟淋巴细胞、但既无巨噬细胞功能障碍也无循环补体减少的scid小鼠中人类HSC的植入，这表明巨噬细胞和/或补体在HSC移植排斥中也起作用。本研究表明，除了抑制T细胞和进行骨髓消融外，对受体NK细胞进行预处理靶向可能会预防HSC移植失败，并且用抗去唾液酸GM1抗血清处理的NOD/Shi - scid小鼠可为评估可移植人类HSC的再增殖能力提供有用的工具。
