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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2002-09-2755. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2755v1 102/3/873    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hiramatsu, H. Articles by Nakahata, T. Search for Related Content PubMed PubMed Citation Articles by Hiramatsu, H. Articles by Nakahata, T. Related Collections Hematopoiesis Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2003, Vol. 102, No. 3, pp. 873-880 HEMATOPOIESIS Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/cnull mice model Hidefumi Hiramatsu, Ryuta Nishikomori, Toshio Heike, Mamoru Ito, Kimio Kobayashi, Kenji Katamura, and Tatsutoshi Nakahata From the Department of Pediatrics, Graduate School of Medicine, Kyoto University; and the Central Institute for Experimental Animals, Kawasaki, Japan 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/ cnull 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 V (TCR V) 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/ cnull mice provide a unique model to investigate human lymphopoiesis without the cotransplantation of human tissues. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Tonomura, K. Habiro, A. Shimizu, M. Sykes, and Y.-G. Yang Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model Blood, April 15, 2008; 111(8): 4293 - 4296. [Abstract] [Full Text] [PDF] S. Watanabe, S. Ohta, M. Yajima, K. Terashima, M. Ito, H. Mugishima, S. Fujiwara, K. Shimizu, M. Honda, N. Shimizu, et al. 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