Growth of primary T-cell non-Hodgkin's lymphomata in SCID-hu mice: requirement for a human lymphoid microenvironment.
Growth of primary T-cell non-Hodgkin's lymphomata in SCID-hu mice: requirement for a human lymphoid microenvironment.
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DOI：
10.1182/blood.v78.10.2650.bloodjournal78102650
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发表时间：
1991-11
期刊：
影响因子：
20.3
通讯作者：
E. Waller;O. Kamel;M. Cleary;A. Majumdar;M. Schick;M. Lieberman;I. Weissman
中科院分区：
文献类型：
--
作者：
E. Waller;O. Kamel;M. Cleary;A. Majumdar;M. Schick;M. Lieberman;I. Weissman
我们推断，SCID-hu小鼠可以提供适当的淋巴或基质微环境，以支持原发性人类淋巴瘤的生长。将9例原发性T细胞非霍奇金淋巴瘤（NHL）异源移植到未经治疗的SCID小鼠和用人胎胸腺、脾和肝重建的SCID小鼠（SCID-hu）中，导致5例（56%）发生淋巴瘤。两个克隆性T细胞NHL生长后，平均90天后，注射到胸腺移植瘤的原发性淋巴瘤细胞悬浮液在SCID-hu小鼠，并未能在SCID小鼠的各种网站的增长，除了小肿瘤，开发后的长（157天）潜伏期后颅内注射肿瘤细胞悬浮液到断奶的SCID小鼠。NHL在SCID和SCID-hu小鼠中的成功连续移植需要人淋巴或肿瘤微环境的存在，并且通过用175 rad辐射和抗asialo抗血清预处理SCID小鼠来增强。通过流式细胞术和固定组织切片的免疫表型分析，原发性和移植性T细胞肿瘤的分析显示T细胞表面标志物的模式相同，并且在一种情况下，与V β 5.1的特异性单克隆抗体反应。移植肿瘤的基因分型显示T细胞受体基因重排与原发性肿瘤中存在的基因重排相同。在一例病例中，在将肿瘤碎片移植到SCID小鼠后，与原发性肿瘤相关的EB病毒阳性B细胞的存在导致淋巴母细胞样B细胞肿瘤的生长以及恶性T细胞淋巴瘤的生长。这些数据支持了人类淋巴微环境增强SCID小鼠中T细胞NHL生长的假设。SCID-hu胸腺移植物提供了一个明显独特的微环境，支持原发性T细胞NHL的生长，并可用于研究体内淋巴瘤细胞，非转化淋巴样细胞和周围基质微环境之间的相互作用。
We reasoned that the SCID-hu mouse could provide an appropriate lymphoid or stromal microenvironment to support the growth of primary human lymphoma. Heterotransplantation of nine cases of primary T-cell non-Hodgkin's lymphoma (NHL) into untreated SCID mice and SCID mice reconstituted with human fetal thymus, spleen, and liver (SCID-hu) resulted in the development of lymphoid tumors in five (56%) cases. Two clonal T-cell NHL grew after a mean of 90 days after injection of primary lymphoma cell suspensions into the thymus xenografts in SCID-hu mice and failed to grow in a variety of sites in SCID mice, except for small tumors that developed after a long (157-day) latency period after intracranial injection of tumor cell suspensions into weanling SCID mice. Successful serial transplantation of NHL in SCID and SCID-hu mice required the presence of a human lymphoid or tumor microenvironment, and was enhanced by pretreating the SCID mice with 175 rad radiation and antiasialo antisera. Analysis of the primary and transplanted T-cell tumors showed identical patterns of T-cell surface markers by flow cytometry and immunophenotyping of fixed tissue sections, and, in one case, reactivity with a specific monoclonal antibody to V beta 5.1. Genotyping of the transplanted tumors showed T-cell receptor gene rearrangements identical to those present in the primary tumors. In one case, the presence of Epstein-Barr virus-positive B cells in association with the primary tumor resulted in the growth of a lymphoblastoid B-cell neoplasm in addition to the malignant T-cell lymphoma after transplantation of tumor fragments to SCID mice. The data support the hypothesis that a human lymphoid microenvironment enhances the growth of T-cell NHL in SCID mice. The SCID-hu thymus graft provides an apparently unique microenvironment that supports the growth of primary T-cell NHL, and can be used to study the interaction between lymphoma cells, nontransformed lymphoid cells, and the surrounding stromal microenvironment in vivo.