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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1565-1573. Prepublished online as a Blood First Edition Paper on May 26, 2005; DOI 10.1182/blood-2005-02-0516. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 2005-02-0516v1 106/5/1565    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 Ishikawa, F. Articles by Harada, M. Search for Related Content PubMed PubMed Citation Articles by Ishikawa, F. Articles by Harada, M. Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Development of functional human blood and immune systems in NOD/SCID/IL2 receptor chainnull mice Fumihiko Ishikawa, Masaki Yasukawa, Bonnie Lyons, Shuro Yoshida, Toshihiro Miyamoto, Goichi Yoshimoto, Takeshi Watanabe, Koichi Akashi, Leonard D. Shultz, and Mine Harada From the Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Japan; The Jackson Laboratory, Bar Harbor, ME; Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan; RIKEN for Allergy and Immunology, Yokohama, Japan; and the Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA. Here we report that a new nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse line harboring a complete null mutation of the common cytokine receptor chain (NOD/SCID/interleukin 2 receptor [IL2r] null) efficiently supports development of functional human hemato-lymphopoiesis. Purified human (h) CD34+ or hCD34+hCD38– cord blood (CB) cells were transplanted into NOD/SCID/IL2rnull newborns via a facial vein. In all recipients injected with 105 hCD34+ or 2 x 104 hCD34+hCD38– CB cells, human hematopoietic cells were reconstituted at approximately 70% of chimerisms. A high percentage of the human hematopoietic cell chimerism persisted for more than 24 weeks after transplantation, and hCD34+ bone marrow grafts of primary recipients could reconstitute hematopoiesis in secondary NOD/SCID/IL2rnull recipients, suggesting that this system can support self-renewal of human hematopoietic stem cells. hCD34+hCD38– CB cells differentiated into mature blood cells, including myelomonocytes, dendritic cells, erythrocytes, platelets, and lymphocytes. Differentiation into each lineage occurred via developmental intermediates such as common lymphoid progenitors and common myeloid progenitors, recapitulating the steady-state human hematopoiesis. B cells underwent normal class switching, and produced antigen-specific immunoglobulins (Igs). T cells displayed the human leukocyte antigen (HLA)–dependent cytotoxic function. Furthermore, human IgA-secreting B cells were found in the intestinal mucosa, suggesting reconstitution of human mucosal immunity. Thus, the NOD/SCID/IL2rnull newborn system might be an important experimental model to study the human hemato-lymphoid system. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Nogami, H. Yoshida, K. Koizumi, H. Yamada, K. Abe, A. Arimura, N. Yamane, K. Takahashi, A. Yamane, A. Oda, et al. The effect of a novel, small non-peptidyl molecule butyzamide on human thrombopoietin receptor and megakaryopoiesis Haematologica, October 1, 2008; 93(10): 1495 - 1504. [Abstract] [Full Text] [PDF] C. Gurer, T. Strowig, F. Brilot, M. Pack, C. Trumpfheller, F. Arrey, C. G. Park, R. M. Steinman, and C. Munz Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses Blood, August 15, 2008; 112(4): 1231 - 1239. [Abstract] [Full Text] [PDF] Y. Kikushige, G. Yoshimoto, T. Miyamoto, T. Iino, Y. Mori, H. Iwasaki, H. Niiro, K. Takenaka, K. Nagafuji, M. 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