Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/gammac-/-, Balb/c-Rag1-/-gammac-/-, and C.B-17-scid/bg immunodeficient mice.
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.
Lepus
Christin M
CM
Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06509, USA.
Gibson
Thomas F
TF
Gerber
Scott A
SA
Kawikova
Ivana
I
Szczepanik
Marian
M
Hossain
Jaber
J
Ablamunits
Vitaly
V
Kirkiles-Smith
Nancy
N
Herold
Kevan C
KC
Donis
Ruben O
RO
Bothwell
Alfred L
AL
Pober
Jordan S
JS
Harding
Martha J
MJ
D000818:Animals; D005312:Fetal Blood / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D007136:Immunoglobulins / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D008099:Liver / Q000196:embryology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D011829:Radiation Dosage; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014916:Whole-Body Irradiation
D007136:Immunoglobulins; D016179:Granulocyte Colony-Stimulating Factor; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin