Improved engraftment of human spleen cells in NOD/LtSz-scid/scid mice as compared with C.B-17-scid/scid mice.
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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发表时间：
1995-04
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通讯作者：
Dale L. Greiner;Leonard D. Shultz;Jon A. Yates;Michael C. Appel;George Perdrizet;R. Hesselton;I. Schweitzer;W. G. Beamer;K. L. Shultz;Stephen C. Pelsue;J. Leif;Thiruchandurai V. Rajan
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作者：
Dale L. Greiner;Leonard D. Shultz;Jon A. Yates;Michael C. Appel;George Perdrizet;R. Hesselton;I. Schweitzer;W. G. Beamer;K. L. Shultz;Stephen C. Pelsue;J. Leif;Thiruchandurai V. Rajan
T和B淋巴细胞缺陷小鼠的严重联合免疫缺陷（SCID）突变纯合子可以与人淋巴细胞免疫移植。然而，通常观察到低水平的人外周血单核细胞植入，阻碍了该模型的充分使用。我们现在证明，scid突变纯合子小鼠的品系背景是人淋巴细胞植入水平的强决定因素。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的植入。我们使用注射人脾细胞的scid小鼠观察到，1）人CD 45+在宿主外周淋巴组织中植入高水平（白细胞）、CD3+（T细胞）、CD4 +（辅助/诱导）和CD8 +在NOD/LtSz-scid/scid小鼠中培养（抑制/细胞毒性）淋巴细胞长达24周;（2）NOD/LtSz-scid/scid小鼠有大量人淋巴细胞向外周淋巴和非淋巴器官迁移，而C. B-17-scid/scid小鼠无此现象; 3）NOD/LtSz-scid/scid小鼠血清中人源免疫球蛋白水平高于C. B-17-scid/scid小鼠：4）NOD/LtSz-scid/scid小鼠组织学病变表现为人源性抗小鼠异种反应;和5）在与天然人脾细胞移植后抗丝虫抗原的人源抗体。使用NOD/LtSz-scid/scid小鼠作为受体，以实现显着增强的人类淋巴细胞移植，现在将使人类免疫更容易在动物模型中进行研究。
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 characteristic of human anti-mouse xenoreactivity in NOD/LtSz-scid/scid mice; and 5), human origin antibodies against filarial antigens after engraftment with native 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.