Monocytes derived from humanized neonatal NOD/SCID/IL2R纬^null mice are phenotypically immature and exhibit functional impairments

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• 作者：Christian Gille^a ; ^&dagger ; ; Thorsten W. Orlikowsky^b ; ^&dagger ; ; Baerbel Spring^a ; Udo F. Hartwig^c ; Ayline Wilhelm^d ; Andreas Wirth^d ; Barbara Goecke^d ; Rupert Handgretinger^d ; Christian F. Poets^a ; Maya C. André ; ^d ; ^e ; ^{maya.andre@med.uni-tuebingen.de}
• 关键词：NOD/SCID/IL2R纬null ; Mouse ; Monocyte ; Neonatal ; Phagocytosis
• 刊名：Human Immunology
• 出版年：2012
• 期刊代码：75_01988859
• 类别：bio
• 出版时间：April, 2012
• 卷：73
• 期：4
• 页码：346-354
• 文件大小：1553 K

摘要

Trials of immune-modulating drugs in septic patients have mostly failed to demonstrate clinical efficacy. Thus, we sought to generate a surrogate model of myelomonocytic lineage differentiation that would potentially allow sepsis induction and preclinical testing of anti-inflammatory drugs. Comparing transplantation of cord blood-derived stem cells in neonatal NOD/SCID/IL2R纬^null (neonatal huNSG) mice with transplantation of adult peripheral mobilized stem cells into adult NSG (adult huNSG) recipients, we demonstrate that myelomonocytic lineage differentiation in neonatal huNSG mice is retarded and monocytes are phenotypically immature with respect to HLA-DR expression and the emergence of CD80⁺CD86⁺ monocytes. Functionally, neonatal huNSG mice were less sensitive toward interferon-纬-induced upregulation of CD86 and exhibited a reduced T-cell stimulating capacity when compared with adult huNSG mice, whereas the phagocytic activity and the ability for cytokine secretion were mature. However, comparison of these data with data obtained from human neonates indicate that absence of the CD80⁺CD86⁺ population and the reduced T-cell stimulating capacity of neonatal huNSG monocytes resemble functional immaturities observed in human neonatal monocytes. Thus, these two mouse models might well serve as 2 independent surrogate models for studying the neonatal myelomonocytic lineage differentiation or for testing the efficacy of immunomodulatory drugs on functionally mature monocytes.