Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models
Akihiro Mori,
Soichiro Murata,
Nao Tashiro,
Tomomi Tadokoro,
Satoshi Okamoto,
Ryo Otsuka,
Haruka Wada,
Tomoki Murata,
Takeshi Takahashi,
Ken-ichiro Seino,
Hideki Taniguchi
Affiliations
Akihiro Mori
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9, Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
Soichiro Murata
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9, Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
Nao Tashiro
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9, Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
Tomomi Tadokoro
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9, Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
Satoshi Okamoto
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9, Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
Ryo Otsuka
Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Sapporo, Hokkaido 060-0815, Japan
Haruka Wada
Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Sapporo, Hokkaido 060-0815, Japan
Tomoki Murata
Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Sapporo, Hokkaido 060-0815, Japan
Takeshi Takahashi
Central Institute for Experimental Animals (CIEA), Kawasaki 210-0821, Japan
Ken-ichiro Seino
Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Sapporo, Hokkaido 060-0815, Japan
Hideki Taniguchi
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9, Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
Humanized mouse models have contributed significantly to human immunology research. In transplant immunity, human immune cell responses to donor grafts have not been reproduced in a humanized animal model. To elicit human T-cell immune responses, we generated immune-compromised nonobese diabetic/Shi-scid, IL-2RγKO Jic (NOG) with a homozygous expression of human leukocyte antigen (HLA) class I heavy chain (NOG-HLA-A2Tg) mice. After the transplantation of HLA-A2 human hematopoietic stem cells into NOG-HLA-A2Tg, we succeeded in achieving alloimmune responses after the HLA-mismatched human-induced pluripotent stem cell (hiPSC)-derived liver-like tissue transplantation. This immune response was inhibited by administering tacrolimus. In this model, we reproduced allograft rejection after the human iPSC-derived liver-like tissue transplantation. Human tissue transplantation on the humanized mouse liver surface is a good model that can predict T-cell-mediated cellular rejection that may occur when organ transplantation is performed.
