Intra-thymic/splenic engraftment of human T cells in HLA-DR1 transgenic NOD/scid mice
Intra-thymic/splenic engraftment of human T cells in HLA-DR1 transgenic NOD/scid mice
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DOI：
10.1016/j.cellimm.2005.02.003
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发表时间：
2004-11-01
影响因子：
4.3
通讯作者：
Koo, GC
中科院分区：
文献类型：
--
作者：
Camacho, RE;Wnek, R;Koo, GC
通过将现有的BIO.M/J-[Tg] DR 1小鼠与NOD/scid小鼠交配，获得HLA-DR 1转基因小鼠（NOD/scid-DR 1）。目的是通过在组织中提供人II类元件来增强人T细胞的植入。将成年NOD/scid-DR 1小鼠的胸腺和脾脏碎片移植到同系肾包膜下，然后将人脐带血单个核细胞（CBMNC）注射到移植组织中。流式细胞仪分析表明，人T和B细胞在嵌合小鼠的外周血和脾脏中始终检测到。在脾脏和移植的胸腺/脾脏组织中发现平均20%的人细胞。此外，来自这些组织的人细胞可以用抗人CD 3抗体增殖，并且这些小鼠可以对同种异体人细胞产生体液和细胞应答。当用同种异体细胞刺激时，在来自嵌合小鼠的培养的人细胞的上清液中也检测到细胞因子，如IL-10、GMCSF、IFN-γ和TNF-α。因此，建立了一种具有功能性循环人类T和B细胞的新型小鼠模型，这将有助于探索疫苗、自身免疫、HIV感染和人类癌症的疾病过程。(c)2005年爱思唯尔公司All rights reserved.
A HLA-DR1 transgenic mouse (NOD/scid-DR1) was derived by breeding the existing BIO.M/J-[Tg]DR1 mouse with the NOD/scid mouse. The intention was to enhance engraftment of human T cells by providing human class II elements in the tissues. Thymus and spleen fragments from adult NOD/scid-DR1 mice were transplanted under the syngeneic kidney capsules, followed by injection of human cord blood mononuclear cells (CBMNC) into transplanted tissues. FACS analyses showed that human T and B cells were consistently detected in the peripheral blood and spleen, of the chimeric mice. An average of 20% of human cells was found in the spleen and the engrafted thymus/spleen tissues. Furthermore, human cells from these tissues could proliferate with anti-human CD3 antibody and these mice could generate humoral and cellular responses to allogeneic human cells. Cytokines, such as IL-10, GMCSF, IFN-gamma and TNF-alpha were also detected in the supernatants of the cultured human cells from the chimeric mice, when they were stimulated with allogeneic cells. Therefore, a novel mouse model with functional circulating human T and B cells was established that would facilitate the exploration of vaccine, the disease processes of autoimmunity, HIV infection, and human cancer. (c) 2005 Elsevier Inc. All rights reserved.