title: Efficient xenoengraftment in severe immunodeficient NOD/Shi-scid IL2rγnull mice is attributed to a lack of CD11c+B220+CD122+ cells.
abstract: Xenograft animal models using immunodeficient mice have been widely applied in medical research on various human diseases. NOD/Shi-scid-IL2rγ(null) (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.
authors.affiliation: Central Institute for Experimental Animals, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Ito
authors.forename: Ikumi
authors.initials: I
authors.lastname: Katano
authors.forename: Miyuki
authors.initials: M
authors.lastname: Ida-Tanaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kamisako
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suemizu
authors.forename: Sadakazu
authors.initials: S
authors.lastname: Aiso
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000096:biosynthesis / Q000235:genetics; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D053631:Interleukin Receptor Common gamma Subunit / Q000096:biosynthesis / Q000172:deficiency*; D053646:Interleukin-2 Receptor beta Subunit / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D039521:CD11c Antigen; C508022:Il2rb protein, mouse; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D053646:Interleukin-2 Receptor beta Subunit; D017493:Leukocyte Common Antigens