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
相关论文
共 35 条
  • [11] Kubo H, 1996, CANCER RES, V56, P2368
  • [12] KYOIZUMI S, 1992, BLOOD, V79, P1704
  • [13] THE SCID DEFECT AFFECTS THE FINAL STEP OF THE IMMUNOGLOBULIN VDJ RECOMBINASE MECHANISM
    MALYNN, BA
    BLACKWELL, TK
    FULOP, GM
    RATHBUN, GA
    FURLEY, AJW
    FERRIER, P
    HEINKE, LB
    PHILLIPS, RA
    YANCOPOULOS, GD
    ALT, FW
    [J]. CELL, 1988, 54 (04) : 453 - 460
  • [14] MCCUNE J, 1991, ANNU REV IMMUNOL, V9, P399, DOI 10.1146/annurev.iy.09.040191.002151
  • [15] SUPPRESSION OF HIV-INFECTION IN AZT-TREATED SCID-HU MICE
    MCCUNE, JM
    NAMIKAWA, R
    SHIH, CC
    RABIN, L
    KANESHIMA, H
    [J]. SCIENCE, 1990, 247 (4942) : 564 - 566
  • [16] THE SCID-HU MOUSE - MURINE MODEL FOR THE ANALYSIS OF HUMAN HEMATOLYMPHOID DIFFERENTIATION AND FUNCTION
    MCCUNE, JM
    NAMIKAWA, R
    KANESHIMA, H
    SHULTZ, LD
    LIEBERMAN, M
    WEISSMAN, IL
    [J]. SCIENCE, 1988, 241 (4873) : 1632 - 1639
  • [17] MCCUNE JM, 1989, CURR TOP MICROBIOL, V152, P183
  • [18] IMMUNODEFICIENT MICE XENOGRAFTED WITH HUMAN LYMPHOID-CELLS - NEW MODELS FOR INVIVO STUDIES OF HUMAN IMMUNOBIOLOGY AND INFECTIOUS-DISEASES
    MOSIER, DE
    [J]. JOURNAL OF CLINICAL IMMUNOLOGY, 1990, 10 (04) : 185 - 191
  • [19] TRANSFER OF A FUNCTIONAL HUMAN IMMUNE-SYSTEM TO MICE WITH SEVERE COMBINED IMMUNODEFICIENCY
    MOSIER, DE
    GULIZIA, RJ
    BAIRD, SM
    WILSON, DB
    [J]. NATURE, 1988, 335 (6187) : 256 - 259
  • [20] HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION OF HUMAN-PBL-SCID MICE
    MOSIER, DE
    GULIZIA, RJ
    BAIRD, SM
    WILSON, DB
    SPECTOR, DH
    SPECTOR, SA
    [J]. SCIENCE, 1991, 251 (4995) : 791 - 794