首页> 美国卫生研究院文献>Journal of the Boston Society of Medical Sciences >Improved Engraftment of Human Spleen Cells in NOD/LtSz-scid/scid Mice as Compared with C.B-17-scid/scid Mice
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Improved Engraftment of Human Spleen Cells in NOD/LtSz-scid/scid Mice as Compared with C.B-17-scid/scid Mice

机译:与C.B-17-scid / scid小鼠相比NOD / LtSz-scid / scid小鼠中人类脾细胞的植入改善

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摘要

T and B lymphocyte-deficient mice homozygous for the severe combined immunodeficiency (SCID) mutation can be immunologically engrafted with human lymphocytes. However, low levels of human peripheral blood mononuclear cell engraftment are commonly observed, impeding full use of this model We now demonstrate that strain background in mice homozygous for the scid mutation is a strong determinant of levels of human lymphocyte engraftment. NOD/LtSz-scid/scid mice support higher levels of engraftment of both human spleen and peripheral blood mononuclear cells than do C.B-17-scid/scid mice. We observed, using human spleen cell injected scid mice, 1), high levels of engraftment of the host peripheral lymphoid tissues with human CD45+ (leukocytes), CD3+ (T cells), CD4+ (helper/inducer), and CD8+ (suppressor/cytotoxic) lymphoid cells for up to 24 weeks in NOD/LtSz-scid/scid mice; 2), migration of high numbers of human lymphocytes to peripheral lymphoid and nonlymphoid organs in NOD/LtSz-scid/scid, but not in C.B-17-scid/scid mice; 3), higher levels of serum immunoglobulin of human origin in NOD/LtSz-scid/scid mice than in C.B-17-scid/scid mice; 4), histological lesions character-istic of human anti-mouse xenoreactivity in NOD/LtSz-scid/scid mice; and 5), human origin antibodies against filarial antigens after engraftment with naive human spleen cells. The use of NOD/LtSz-scid/scid mice as recipients to achieve significantly enhanced human lymphopoietic cell engraftment will now enable human immunity to be more easily studied in animal models.
机译:对于严重的联合免疫缺陷症(SCID)突变纯合的T和B淋巴细胞缺陷型小鼠可以免疫接种人类淋巴细胞。但是,通常观察到低水平的人类外周血单个核细胞植入,阻碍了该模型的充分利用。我们现在证明,scid突变纯合子的小鼠品系背景是人类淋巴细胞植入水平的重要决定因素。 NOD / LtSz-scid / scid小鼠比C.B-17-scid / scid小鼠支持更高水平的人脾和外周血单核细胞移植。我们观察到,使用人类脾细胞注射的scid小鼠,1)高水平植入了宿主CD45 + (白细胞),CD3 + (T细胞),CD4 + (辅助/诱导物)和CD8 + (抑制子/细胞毒性)淋巴样细胞在NOD / LtSz-scid / scid小鼠中长达24周; 2)在NOD / LtSz-scid / scid小鼠中大量人淋巴细胞向外周淋巴和非淋巴器官迁移,而在C.B-17-scid / scid小鼠中则没有。 3),NOD / LtSz-scid / scid小鼠的人源血清免疫球蛋白水平高于C.B-17-scid / scid小鼠; 4),NOD / LtSz-scid / scid小鼠中人抗小鼠异种反应的组织学损伤特征;和5),在植入人幼稚脾细胞后针对丝状抗原的人源抗体。现在,使用NOD / LtSz-scid / scid小鼠作为受体来显着增强人类淋巴细胞的细胞植入将使人类免疫性更容易在动物模型中进行研究。

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