Efficient Xenoengraftment in Severe Immunodeficient NOD/Shi-scid IL2rγnull Mice Is Attributed to a Lack of CD11c+B220+CD122+ Cells
Efficient Xenoengraftment in Severe Immunodeficient NOD/Shi-scid IL2rγnull Mice Is Attributed to a Lack of CD11c+B220+CD122+ Cells
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DOI：
10.4049/jimmunol.1200820
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发表时间：
2012-11-01
影响因子：
4.4
通讯作者：
Ito, Mamoru
中科院分区：
文献类型：
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作者：
Ito, Ryoji;Katano, Ikumi;Ito, Mamoru
免疫缺陷小鼠异种移植动物模型已广泛应用于各种人类疾病的医学研究。与常规免疫缺陷小鼠相比，NOD/Shi-scid-IL2r γ (null) （NOG）小鼠显示出极高的异种移植移植率。NOG小鼠中异种移植的高移植率被缺乏NK细胞的NOD-scid小鼠脾细胞的转移大大抑制。这些结果表明，NOD-scid小鼠中存在而NOG小鼠中不存在脾脏NK细胞以外的细胞类型可能参与了这种抑制。为了确定导致这种效果的细胞类型，我们将NOD-scid小鼠的脾细胞亚群转移到NOG小鼠中，并评估了人PBMC （hPBMC）移植后的人细胞植入水平。这些实验表明，NOD-scid小鼠的CD11c(+)B220（+）浆细胞样树突状细胞（pDCs）明显抑制人细胞的移植。CD11c(+)B220(+) CD122（+）细胞通过表达CD122进一步从pDCs中分离出来。CD122是一种NK细胞标记物，在NOG小鼠的hPBMC植入过程中被强烈抑制。此外，pDC组分中的CD122（+）细胞在形态上与常规CD122(+) NK细胞不同，并表现出更高的排斥效率。目前的研究结果表明，CD11c(+)B220(+) CD122（+）细胞在异种移植排斥反应中起重要作用，而它们在NOG小鼠中的缺失可能是支持异种移植成功的关键。中国生物医学工程学报，2012,33(2):432 -432。
Xenograft animal models using immunodeficient mice have been widely applied in medical research on various human diseases. NOD/Shi-scid-IL2r gamma(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. The Journal of Immunology, 2012, 189: 4313-4320.