Efficient xenoengraftment in severe immunodeficient NOD/Shi-scid IL2rγnull mice is attributed to a lack of CD11c +B220+CD122+ cells

Ryoji Ito, Ikumi Katano, Miyuki Ida-Tanaka, Tsutomu Kamisako, Kenji Kawai, Hiroshi Suemizu, Sadakazu Aiso, Mamoru Ito

Research output: Contribution to journalArticle

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Abstract

Xenograft animal models using immunodeficient mice have been widely applied in medical research on various human diseases. NOD/Shi-scid -IL2rγnull (NOG) mice are known to show an extremely high engraftment rate of xenotransplants compared with conventional immunodeficient mice. This high engraftment rate of xenotransplants in NOG mice was substantially suppressed by the transfer of spleen cells from NOD-scid mice that were devoid of NK cells. These results indicate that cell types other than splenic NK cells present in NOD- scid mice but not in NOG mice may be involved in this suppression. To identify the cell types responsible for this effect, we transferred subpopulations of spleen cells from NOD-scid mice into NOG mice and assessed the levels of human cell engraftment after human PBMC (hPBMC) transplantation. These experiments revealed that CD11c+B220 + plasmacytoid dendritic cells (pDCs) from NOD-scid mice markedly inhibited engraftment of human cells. The CD11c+B220+ CD122+ cells further fractionated from the pDCs based on the expression of CD122, which is an NK cell marker strongly inhibited during hPBMC engraftment in NOG mice. Moreover, the CD122+ cells in the pDC fraction were morphologically distinguishable from conventional CD122 + NK cells and showed a higher rejection efficiency. The current results suggest that CD11c+B220+ CD122+ cells play an important role in xenograft rejection, and their absence in NOG mice may be critical in supporting the successful engraftment of xenotransplants.

Original languageEnglish
Pages (from-to)4313-4320
Number of pages8
JournalJournal of Immunology
Volume189
Issue number9
DOIs
Publication statusPublished - 2012 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

Cite this

Efficient xenoengraftment in severe immunodeficient NOD/Shi-scid IL2rγnull mice is attributed to a lack of CD11c +B220+CD122+ cells. / Ito, Ryoji; Katano, Ikumi; Ida-Tanaka, Miyuki; Kamisako, Tsutomu; Kawai, Kenji; Suemizu, Hiroshi; Aiso, Sadakazu; Ito, Mamoru.

In: Journal of Immunology, Vol. 189, No. 9, 01.11.2012, p. 4313-4320.

Research output: Contribution to journalArticle

Ito, Ryoji ; Katano, Ikumi ; Ida-Tanaka, Miyuki ; Kamisako, Tsutomu ; Kawai, Kenji ; Suemizu, Hiroshi ; Aiso, Sadakazu ; Ito, Mamoru. / Efficient xenoengraftment in severe immunodeficient NOD/Shi-scid IL2rγnull mice is attributed to a lack of CD11c +B220+CD122+ cells. In: Journal of Immunology. 2012 ; Vol. 189, No. 9. pp. 4313-4320.
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abstract = "Xenograft animal models using immunodeficient mice have been widely applied in medical research on various human diseases. NOD/Shi-scid -IL2rγnull (NOG) mice are known to show an extremely high engraftment rate of xenotransplants compared with conventional immunodeficient mice. This high engraftment rate of xenotransplants in NOG mice was substantially suppressed by the transfer of spleen cells from NOD-scid mice that were devoid of NK cells. These results indicate that cell types other than splenic NK cells present in NOD- scid mice but not in NOG mice may be involved in this suppression. To identify the cell types responsible for this effect, we transferred subpopulations of spleen cells from NOD-scid mice into NOG mice and assessed the levels of human cell engraftment after human PBMC (hPBMC) transplantation. These experiments revealed that CD11c+B220 + plasmacytoid dendritic cells (pDCs) from NOD-scid mice markedly inhibited engraftment of human cells. The CD11c+B220+ CD122+ cells further fractionated from the pDCs based on the expression of CD122, which is an NK cell marker strongly inhibited during hPBMC engraftment in NOG mice. Moreover, the CD122+ cells in the pDC fraction were morphologically distinguishable from conventional CD122 + NK cells and showed a higher rejection efficiency. The current results suggest that CD11c+B220+ CD122+ cells play an important role in xenograft rejection, and their absence in NOG mice may be critical in supporting the successful engraftment of xenotransplants.",
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AU - Katano, Ikumi

AU - Ida-Tanaka, Miyuki

AU - Kamisako, Tsutomu

AU - Kawai, Kenji

AU - Suemizu, Hiroshi

AU - Aiso, Sadakazu

AU - Ito, Mamoru

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