| Literature DB >> 19524633 |
Christin M Lepus1, Thomas F Gibson, Scott A Gerber, Ivana Kawikova, Marian Szczepanik, Jaber Hossain, Vitaly Ablamunits, Nancy Kirkiles-Smith, Kevan C Herold, Ruben O Donis, Alfred L Bothwell, Jordan S Pober, Martha J Harding.
Abstract
Immunodeficient mice bearing components of a human immune system present a novel approach for studying human immune responses. We investigated the number, phenotype, developmental kinetics, and function of developing human immune cells following transfer of CD34(+) hematopoietic stem cell (HSC) preparations originating from second trimester human fetal liver (HFL), umbilical cord blood (UCB), or granulocyte colony-stimulating factor-mobilized adult blood (G-CSF-AB) delivered via intrahepatic injection into sublethally irradiated neonatal NOD-scid/gammac(-/-), Balb/c-Rag1(-/-)gammac(-/-), and C.B-17-scid/bg mice. HFL and UCB HSC provided the greatest number and breadth of developing cells. NOD-scid/gammac(-/-) and Balb/c-Rag1(-/-)gammac(-/-) harbored human B and dendritic cells as well as human platelets in peripheral blood, whereas NOD-scid/gammac(-/-) mice harbored higher levels of human T cells. NOD-scid/gammac(-/-) mice engrafted with HFL CD34(+) HSC demonstrated human immunological competence evidenced by white pulp expansion and increases in total human immunoglobulin following immunization with T-dependent antigens and delayed-type hypersensitivity-infiltrating leukocytes in response to antigenic challenge. In conclusion, we describe an encouraging base system for studying human hematopoietic lineage development and function utilizing human HFL or UCB HSC-engrafted NOD-scid/gammac(-/-) mice that is well suited for future studies toward the development of a fully competent humanized mouse model.Entities:
Mesh：
Substances：
Year: 2009 PMID： 19524633 PMCID： PMC2949440 DOI： 10.1016/j.humimm.2009.06.005
Source DB: PubMed Journal: Hum Immunol ISSN： 0198-8859 Impact factor: 2.850