Anti-NK cell treatment induces stable mixed chimerism in MHC-mismatched, T cell-depleted, nonmyeloablative bone marrow transplantation
Anti-NK cell treatment induces stable mixed chimerism in MHC-mismatched, T cell-depleted, nonmyeloablative bone marrow transplantation
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DOI：
10.1016/j.exphem.2004.08.008
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发表时间：
2004-12-01
影响因子：
2.6
通讯作者：
Asano, S
中科院分区：
文献类型：
--
作者：
Cho, SG;Shuto, Y;Asano, S
Objective.为了阐明自然杀伤（NK）细胞介导的细胞减灭条件下的耐药性和T细胞耗竭骨髓移植，我们研究了宿主NK细胞耗竭对植入和诱导稳定混合嵌合体的影响。BALB/c小鼠（H-2k（d））在第-1天腹膜内注射抗去唾液酸GM 1抗体（抗NK Ab）。在第0天，它们接受500 cGy剂量的全身照射（TBI），随后静脉输注来自C57 BL/6小鼠（H-2k（B））的2 × 10（7）T细胞去除（TCD）骨髓细胞。通过第+21天表达H-2k（d）或H-2k（B）的外周血（PB）淋巴细胞的相对比率确定早期植入和嵌合状态。流式细胞术检测PB和脾脏的长期植入和嵌合情况。尽管单独接受TBI治疗的受体均未显示植入，但所有接受抗NK Ab和TBI处理的受体均显示成功植入，以及PB和脾脏中混合嵌合体的供体主导模式。来自混合嵌合体受体的脾细胞对宿主和供体菌株均表现出特异性耐受，但对第三方（C3 H/He）不表现出特异性耐受。所有重建小鼠均未出现移植物抗宿主病的体征，且均存活至+330天。这些观察结果表明，宿主NK细胞耗竭可用于降低TCD移植物植入的预处理方案的强度，并有助于在主要组织相容性复合物不匹配的非清髓性移植中建立稳定的混合嵌合体。(C)2004年国际实验血液学学会。爱思唯尔公司出版
Objective. To clarify natural killer (NK) cell-mediated resistance under cytoreductive conditioning and T cell-depleted bone marrow transplantation, we investigated the effects of host NK cell depletion on engraftment and induction of stable mixed chimerism.Methods. BALB/c mice (H-2k(d)) were injected intraperitoneally with anti-asialoGM1 antibody (anti-NK Ab) on day -1. On day 0, they received total body irradiation (TBI) at a dose of 500 cGy, followed by intravenous infusion of 2 x 10(7) T cell-depleted (TCD) bone marrow cells from C57BL/6 mice (H-2k(b)). Early engraftment and chimerism were determined by the relative ratio of peripheral blood (PB) lymphocytes expressing either H-2k(d) or H-2k(b) on day +21. Long-term engraftment and chimerism were evaluated on PB and spleen by multicolor flow cytometry.Results. Although no recipients treated with TBI alone showed engraftment, all the recipients conditioned with anti-NK Ab and TBI showed successful engraftment as well as a donor-dominant pattern of mixed chimerism in both PB and spleen. Spleen cells from recipients with mixed chimerism showed specific tolerance to both host and donor strains, but not to a third party (C3H/He). None of the reconstituted mice showed signs of graft vs host disease, and all survived up to day +330.Conclusion. These observations indicate that host NK cell depletion may be used to reduce the intensity of conditioning regimens for engraftment of TCD grafts, and can contribute to establishment of stable mixed chimerism in major histocompatibility complex-mismatched nonmyeloablative transplantation. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.