Tumor Necrosis Factor Promotes Human T‐Cell Development in Nonobese Diabetic/Severe Combined Immunodeficient Mice
Tumor Necrosis Factor Promotes Human T‐Cell Development in Nonobese Diabetic/Severe Combined Immunodeficient Mice
复制标题
肿瘤坏死因子促进非肥胖糖尿病/严重联合免疫缺陷小鼠的人类 T 细胞发育
作者：
S. Samira;C. Ferrand;A. Peled;A. Nagler;Y. Tovbin;H. Ben‐Hur;N. Taylor;A. Globerson;T. Lapidot
临床造血干细胞移植后的一个主要问题是T细胞重建不良。研究这一问题背后的机制受到了阻碍，因为将人类干细胞和祖细胞移植到非肥胖糖尿病/严重联合免疫缺陷 (NOD/SCID) 小鼠中的实验通常会导致 T 淋巴细胞重建水平较低。由于肿瘤坏死因子 α (TNFα) 已被认为在体外 T 谱系定型和分化中发挥作用，因此我们研究了其在体内增强人类 T 细胞发育的潜力。在移植来自脐带血或成人 G-CSF 动员的外周血 (MPBL) 的人类单核细胞之前，对受辐射的 NOD/SCID 小鼠施用 TNF，导致移植后 2-3 周在骨髓 (BM)、脾脏和胸腺中出现人类未成熟的 CD4+CD8+ 双阳性 T 细胞，并且在该器官中，人类细胞也表达 CD1a 标记物。一到两周后，在所有三个器官中均检测到表达异源 T 细胞受体 αβ 的单阳性 CD4+ 和 CD8+ 细胞。这些细胞还能够通过血液循环迁移。有趣的是，这些小鼠中人类 T 细胞的发育与小鼠 BM 中未成熟淋巴人类 CD19+ B 细胞和自然杀伤祖细胞的显着减少有关。人类T细胞主要来源于移植的未成熟CD34+细胞。这项研究证明了 TNF 在体内快速增强人 T 淋巴细胞生成的潜力，并为成人 MPBL 祖细胞的这一过程提供了临床相关证据。
A major problem after clinical hematopoietic stem cell transplantations is poor T‐cell reconstitution. Studying the mechanisms underlying this concern is hampered, because experimental transplantation of human stem and progenitor cells into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice usually results in low T–lymphocyte reconstitution. Because tumor necrosis factor α (TNFα) has been proposed to play a role in T‐lineage commitment and differentiation in vitro, we investigated its potential to augment human T‐cell development in vivo. Administration of TNF to irradiated NOD/SCID mice before transplantation of human mononuclear cells from either cord blood or adult G‐CSF–mobilized peripheral blood (MPBL) led 2–3 weeks after transplantation to the emergence of human immature CD4+CD8+ double‐positive T‐cells in the bone marrow (BM), spleen, and thymus, and in this organ, the human cells also express CD1a marker. One to 2 weeks later, single‐positive CD4+ and CD8+ cells expressing heterogenous T‐cell receptor αβ were detected in all three organs. These cells were also capable of migrating through the blood circulation. Interestingly, human T‐cell development in these mice was associated with a significant reduction in immature lymphoid human CD19+ B cells and natural killer progenitors in the murine BM. The human T cells were mostly derived from the transplanted immature CD34+ cells. This study demonstrates the potential of TNF to rapidly augment human T lymphopoiesis in vivo and also provides clinically relevant evidence for this process with adult MPBL progenitors.
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动员的人 CD34+ 外周血祖细胞在 NOD/LtSz-scid/scid 小鼠中进行多谱系移植。
DOI：
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发表时间：
1997
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Hogan,CJ;Shpall,EJ;McNiece,I;Keller,G
通讯作者：
Keller,G
影响因子：
11.2
作者：
K. Tsukasaki;C. W. Miller;T. Kubota;S. Takeuchi;T. Fujimoto;S. Ikeda;M. Tomonaga;H. Koeffler-H.-K
通讯作者：
K. Tsukasaki;C. W. Miller;T. Kubota;S. Takeuchi;T. Fujimoto;S. Ikeda;M. Tomonaga;H. Koeffler-H.-K
影响因子：
20.3
作者：
Pflumio, F;Izac, B;Coulombel, L
通讯作者：
Coulombel, L
影响因子：
20.3
作者：
Cashman, JD;Lapidot, T;Eaves, CJ
通讯作者：
Eaves, CJ
影响因子：
20.3
作者：
C. Hogan;E. Shpall;Oren McNulty;I. Mcniece;J. Dick;L. Shultz;G. Keller
通讯作者：
C. Hogan;E. Shpall;Oren McNulty;I. Mcniece;J. Dick;L. Shultz;G. Keller