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/γc-/-, Balb/c-Rag1-/-γc-/-, and C.B-17-scid/bg mice. HFL and UCB HSC provided the greatest number and breadth of developing cells. NOD-scid/γc-/- and Balb/c-Rag1-/-γc-/- harbored human B and dendritic cells as well as human platelets in peripheral blood, whereas NOD-scid/γc-/- mice harbored higher levels of human T cells. NOD-scid/γc-/- 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/γc-/- mice that is well suited for future studies toward the development of a fully competent humanized mouse model.
- Delayed-type hypersensitivity
- Hematopoietic stem cell
- Human immune system development
- Isotype switching
- Mouse model
ASJC Scopus subject areas
- Immunology and Allergy