Dominant expansion of human T cells in non-obese diabetic/severe combined immunodeficiency mice implanted with human bone fragments

被引:6
作者
Fujiki, Y
Onodera, M
Yamaguchi, T
Osawa, M
Sudo, K
Hamada, H
Ema, H
Shibuya, A
Takiguchi, M
Kubo, T
Nakauchi, H
机构
[1] Univ Tsukuba, Inst Basic Med Sci, Dept Immunol, Tsukuba, Ibaraki 3058575, Japan
[2] Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 3058575, Japan
[3] Japan Sci & Technol Corp, CREST, Tsukuba, Ibaraki, Japan
[4] Univ Tsukuba, Inst Clin Med, Dept Obstet & Gynecol, Tsukuba, Ibaraki 305, Japan
[5] Kumamoto Univ, Ctr AIDS Res, Div Viral Immunol, Kumamoto, Japan
基金
日本学术振兴会;
关键词
bone fragment; NOD/SCID; human T lymphopoiesis; HIV infection; animal model;
D O I
10.1016/S0301-472X(00)00178-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To establish an in vivo animal model in which human T cells develop and function normally, a step toward developing new vaccines or chemical compounds that modulate immune functions and toward understanding T-cell immunity in humans. Materials and Methods. Human bone fragments were implanted into non-obese diabetes / severe combined immunodeficiency (NOD/SCID) mice. The presence of human blood cells in the peripheral blood of these mice was monitored periodically by immunostaining and fluorescence-activated cell sorting. Results. After implantation of bone fragments, dominant expansion of human T lymphocytes, rather than myeloid and B cells, was observed over a 3-month period. In some cases, the proportion of human T cells rose to 40% of the peripheral blood mononuclear cells, These T cells showed CD4/CD8 ratios similar to those observed in human peripheral blood lymphocytes and had a broad repertoire of rearranged T-cell receptor genes. Craft-versus-host reaction was not noted in any organ analyzed. To assess the suitability of NOD/SCID mice implanted with human bone fragments (hu-bone-NOD/SCID mice) as an in vivo model for HIV infection, the mice were infected with a T-lymphotropic strain of HIV-1 (NL4-3) at 7 weeks posttransplant. Serum p24 gag was detected at 2 weeks after inoculation, after which total CD4-positive cell numbers declined, as seen clinically in patients infected with HIV. Conclusion. Although the precise mechanism is yet to be determined by which predominant expansion of human T cells occurs in hu-bone-NOD/SCID mice, such mice appear likely to serve as a useful and versatile model for studies involving human T-cell immunity. (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc.
引用
收藏
页码:792 / 801
页数:10
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