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


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. Graft-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.


CONCLUSIONS
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.
Fujiki
Y
Y
Department of Immunology, Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba and CREST, Japan Science and Technology Corporation, Ibaraki.
Onodera
M
M
Yamaguchi
T
T
Osawa
M
M
Sudo
K
K
Hamada
H
H
Ema
H
H
Shibuya
A
A
Takiguchi
M
M
Kubo
T
T
Nakauchi
H
H
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D016025:Bone Transplantation; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D004195:Disease Models, Animal; D015658:HIV Infections / Q000097:blood; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D019891:Leukopoiesis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000502:physiology* / Q000821:virology; D014162:Transfection
D015704:CD4 Antigens; D016827:CD8 Antigens