Donor gamma delta T lymphocytes promote allogeneic engraftment across the major histocompatibility barrier in mice
Donor gamma delta T lymphocytes promote allogeneic engraftment across the major histocompatibility barrier in mice
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DOI：
10.1182/blood.v89.3.1100
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发表时间：
1997-02-01
期刊：
影响因子：
20.3
通讯作者：
Majewski, D
中科院分区：
文献类型：
--
作者：
Drobyski, WR;Majewski, D
表达α β T细胞受体的T细胞被认为是主要负责促进同种异体移植的T细胞群体。然而，仅包含少数成熟T细胞的γ δ（+）T细胞在促进同种异体移植中的作用尚未得到广泛研究。本研究的目的是确定γ δ T细胞是否能够促进主要组织相容性复合物不匹配的骨髓移植物的小鼠受体的同种异体移植。我们开发了一种模型，其中C57 BL/6 x 129/F2（H-2（B））骨髓在亚致死剂量照射（800 cGy）受体（AKR/J，H-2（k））中的植入依赖于骨髓移植物中成熟供体T细胞的存在。在该模型中，供体T细胞植入显著增加了少至1 × 10（5）杯T细胞。然后使用转基因供体（C57 BL/6 × 129背景）研究γ δ T细胞的作用，其中通过基因靶向缺失T细胞受体β链基因的一部分，使得这些小鼠缺乏α β T细胞。尽管供体T细胞平均100天完全供体植入，但需要向T细胞耗尽的骨髓移植物中添加10 × 10 6个初始γ δ T细胞以显著增加同种异体植入，这表明骨髓移植物中需要有限数量的α β T细胞以根除残留的宿主T细胞。使用系列重量曲线和B细胞重建作为终点，在这些实验条件下，在这些嵌合体中未观察到临床显著的移植物抗宿主病。这些数据表明，虽然不如α β T细胞有效，但γ δ T细胞能够促进同种异体骨髓移植受体的植入并增强造血重建。(C)1997年，美国血液学会。
T cells that express the alpha beta T-cell receptor are thought to be the T-cell population primarily responsible for facilitating alloengraftment. The role of gamma delta(+) T cells that comprise only a minority of mature T cells in promoting allogeneic engraftment, however, has not been extensively studied. The purpose of this study was to determine whether gamma delta T cells were capable of facilitating alloengraftment in murine recipients of major histocompatibility complex-mismatched marrow grafts. We developed a model where engraftment of C57BL/6 x 129/F2 (H-2(b)) marrow in sublethally irradiated (800 cGy) recipients (AKR/J, H-2(k)) is dependent on the presence of mature donor T cells in the marrow graft. In this model, donor T-cell engraftment was significantly augmented by as few as 1 x 10(5) cup T cells. The role of gamma delta T cells was then investigated using transgenic donors (C57BL/6 x 129 background) in which a portion of the T-cell receptor-beta chain gene was deleted by gene targeting so that these mice lack alpha beta T cells. Addition of 10 x 10(6) naive gamma delta T cells to T-cell depleted marrow grafts was required to significantly increase alloengraftment, although donor T cells averaged 100 day) complete donor engraftment, indicating that limiting numbers of alpha beta T cells were required in the marrow graft for the eradication of residual host T cells. Using serial weight curves and B-cell reconstitution as end points, clinically significant graft-versus-host disease was not observed in these chimeras under these experimental conditions. These data show that, whereas less potent than alpha beta T cells, gamma delta T cells are able to promote engraftment and enhance hematopoietic reconstitution in allogeneic marrow transplant recipients. (C) 1997 by The American Society of Hematology.