Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation.
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 cotransplantation of human fetal thymus/liver tissues and CD34(+) hematopoietic stem/progenitor cells led 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.
Lan
Ping
P
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, 02129, USA.
Tonomura
Noriko
N
Shimizu
Akira
A
Wang
Shumei
S
Yang
Yong-Guang
YG
D000818:Animals; D000917:Antibody Formation; D018952:Antigens, CD34; D017690:Cell Transplantation / Q000379:methods*; D005333:Fetus / Q000166:cytology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000502:physiology*; D008099:Liver / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D013950:Thymus Gland / Q000166:cytology*; D014183:Transplantation, Heterologous
D018952:Antigens, CD34