Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/γcnull mice model
Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/γcnull mice model
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DOI：
10.1182/blood-2002-09-2755
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发表时间：
2003-08-01
期刊：
影响因子：
20.3
通讯作者：
Nakahata, T
中科院分区：
文献类型：
--
作者：
Hiramatsu, H;Nishikomori, R;Nakahata, T
建立能够从造血干细胞（HSC）生成所有类别的人类淋巴细胞的测定方法将为人类淋巴细胞生成机制提供新的见解。我们报告了移植人脐带血（CB）CD34（+）细胞后NOD/SCID/gamma（c）（null）小鼠中重建的人淋巴细胞的个体发生、功能和组织学检查结果。移植后，即使没有共同移植人类组织，这些小鼠中仍然能够鉴定出人类 B 细胞、自然杀伤细胞 (NK) 和 T 细胞。未成熟的 B 细胞主要存在于骨髓 (BM) 中，而具有表面免疫球蛋白的成熟 B 细胞优先存在于脾脏中。在骨髓和脾脏中鉴定出 NK 细胞。在各种淋巴器官中都观察到了 T 细胞，但移植后的系列检查证实了胸腺中发生了人类 T 淋巴细胞生成。这些人类淋巴细胞也具有功能。在这些小鼠的血清中检测到人免疫球蛋白 M (IgM)、IgA 和 IgG。 T 细胞表现出多种 T 细胞受体 Vbeta (TCR Vbeta) 链，在植物血凝素的作用下增殖，并对细胞系具有细胞毒性。使用 K562 细胞系证明了 NK 活性。免疫组织化学分析表明，人类淋巴细胞在脾脏和胸腺中形成了与人类相似的组织结构。在胸腺中，CD4 和 CD8 双阳性 T 细胞占主导地位，并共表达 CD1a 和 Ki-67，从而支持 T 淋巴细胞生成的观点。 NOD/SCID/gamma(c)(null) 小鼠提供了一种独特的模型来研究人类淋巴细胞生成，而无需共同移植人体组织。
Establishment of an assay capable of generating all classes of human lymphocytes from hematopoietic stem cells (HSCs) will provide new insight into the mechanism of human lymphopoiesis. We report ontogenic, functional, and histologic examination results of reconstituted human lymphocytes in NOD/SCID/gamma(c)(null) mice after the transplantation of human cord blood (CB) CD34(+) cells. After transplantation, human B, natural killer (NK), and T cells were invariably identified in these mice, even though no human tissues were cotransplanted. Immature B cells resided mainly in bone marrow (BM), whereas mature B cells with surface immunoglobulins were preferentially found in spleen. NK cells were identified in BM and spleen. T cells were observed in various lymphoid organs, but serial examinations after transplantation confirmed human T lymphopoiesis occurring in the thymus. These human lymphocytes were also functionally competent. Human immunoglobulin M (IgM), IgA, and IgG were detected in the sera of these mice. T cells showed a diverse repertoire of T-cell-receptor Vbeta (TCR Vbeta) chains, proliferated in response to phytohemagglutinin, and were cytotoxic against cell lines. NK activity was demonstrated using the K562 cell line. Immunohistochemical analysis revealed that human lymphocytes formed organized structures in spleen and thymus that were analogous to those seen in humans. In the thymus, CD4 and CD8 double-positive T cells were predominant and coexpressed CD1a and Ki-67, thereby supporting the notion that T lymphopoiesis was taking place. NOD/SCID/gamma(c)(null) mice provide a unique model to investigate human lymphopoiesis without the cotransplantation of human tissues.