Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/γc-/-, Balb/c-Rag1-/-γc-/-, and C.B-17-scid/bg immunodeficient mice

被引：96

作者：

Lepus, Christin M. ^{[1
]}

Gibson, Thomas F. ^{[2
]}

Gerber, Scott A. ^{[2
]}

Kawikova, Ivana ^{[2
]}

Szczepanik, Marian ^{[3
,4
]}

Hossain, Jaber ^{[5
]}

Ablamunits, Vitaly ^{[2
]}

Kirkiles-Smith, Nancy ^{[2
]}

Herold, Kevan C. ^{[2
]}

Donis, Ruben O. ^{[5
]}

Bothwell, Alfred L. ^{[2
]}

Pober, Jordan S. ^{[2
,6
,7
]}

Harding, Martha J. ^{[1
]}

机构：

[1] Yale Univ, Comparat Med Sect, Sch Med, New Haven, CT 06509 USA

[2] Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06509 USA

[3] Dept Human Dev Biol, Krakow, Poland

[4] Jagiellonian Univ, Coll Med, Krakow, Poland

[5] Ctr Dis Control, Influenza Div, Atlanta, GA 30333 USA

[6] Yale Univ, Dept Pathol, Sch Med, New Haven, CT 06509 USA

[7] Yale Univ, Dept Dermatol, Sch Med, New Haven, CT 06509 USA

来源：

HUMAN IMMUNOLOGY | 2009年 / 70卷 / 10期

关键词：

Hematopoietic stem cell; Mouse model; Human immune system development; Delayed-type hypersensitivity; Isotype switching; MOUSE MODEL; HUMAN-LYMPHOCYTES; RHEUMATOID-FACTOR; IMMUNE-SYSTEM; CD34(+) CELLS; GAMMA; RESPONSES; ANTIBODIES; VIRUS; AUTOANTIBODIES;

D O I：

10.1016/j.humimm.2009.06.005

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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/gamma c(-/-), Balb/c-Rag1(-/-)gamma c(-/-), and C.B-17-scid/bg mice. HFL and UCB HSC provided the greatest number and breadth of developing cells. NOD-scid/gamma c(-/-) and Balb/c-Rag1(-/-)gamma c(-/-) harbored human B and dendritic cells as well as human platelets in peripheral blood, whereas NOD-scid/gamma c(-/-) mice harbored higher levels of human T cells. NOD-scid/gamma c(-/-) 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/gamma c(-/-) mice that is well suited for future studies toward the development of a fully competent humanized mouse model. (C) 2009 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

引用

页码：790 / 802

页数：13

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