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Blood, 15 July 2006, Vol. 108, No. 2, pp. 487-492. Prepublished online as a Blood First Edition Paper on January 12, 2006; DOI 10.1182/blood-2005-11-4388.
Submitted November 7, 2005
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA * Corresponding author; email: yongguang.yang{at}tbrc.mgh.harvard.edu.
Studies of the human immune system have been limited by the lack of an appropriate in vivo model. For this reason, efforts have been made to develop murine models with a functional human immune system. We report here that co-transplantation of human fetal thymus/liver tissues and CD34+ hematopoietic stem/progenitor cells lead to the development of sustained human hematopoiesis and a functional human immune system in immunodeficient NOD/SCID mice. The humanized mice showed systemic repopulation with a comprehensive array of human lymphohematopoietic cells, including T cells, B cells, and dendritic cells, and the formation of secondary lymphoid organs. Furthermore, these mice produce high levels of human IgM and IgG antibodies and mediate strong immune responses in vivo as demonstrated by skin xenograft rejection. Thus, the humanized NOD/SCID mice described in this paper provide a powerful model system to study human immune function.
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