Regulation of the earliest immune response to in utero hematopoietic cellular transplantation.

Regulation of the earliest immune response to in utero hematopoietic cellular transplantation.
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DOI:
10.4161/chim.1.2.13147
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发表时间:
2010-10-01
期刊:
Chimerism
影响因子:
--
通讯作者:
Shaaban, Aimen F
Shaaban, Aimen F
中科院分区:
其他
文献类型:
--
作者:
Alhajjat, Amir M;Durkin, Emily T;Shaaban, Aimen F

文献摘要

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在子宫造血细胞移植(IUHCT)是一种很有前途的干预措施,以治疗各种先天性疾病。通过将供体细胞提供给未成熟的免疫系统,可以实现混合造血嵌合体和供体特异性耐受。然而,在不存在免疫缺陷的产前受者中,移植失败表明对移植存在胎儿免疫屏障。虽然可能的障碍包括适应性免疫系统和先天免疫系统的效应者,但我们最近的发现和正在进行的研究表明,障碍很可能存在于发育中的NK细胞。在NK细胞发育过程中,嵌合体水平高于一定的阈值是克服排斥反应所必需的。在临床上,这种移植屏障可能也存在于早期的人胎儿NK细胞中。了解胎儿对同种异体移植的免疫屏障对于推进IUHCT的临床应用具有重要意义。在此,我们为产前移植的最早免疫反应提供一个简短的总结和新的证据。
In Utero Hematopoietic Cellular Transplantation (IUHCT) is a promising intervention to treat a wide range of congenital disease. Through the presentation of donor cells to the immature immune system, mixed hematopoietic chimerism and donor-specific tolerance can be achieved. However, the failure of engraftment in prenatal recipients in which no immunodeficiency exists suggests the existence of a fetal immune barrier to transplantation. Although the possible barriers include effectors of the adaptive and innate immune system, our recent findings and ongoing investigations indicate that the barrier most likely resides in the developing NK cells. A chimerism level above a certain threshold during NK cell development is necessary to overcome rejection. Clinically, this transplantation barrier might also exist in early human fetal NK cells. Understanding the fetal immune barrier to allotransplantation is essential in advancing clinical application of IUHCT. Herein, we provide a short summary and new evidence for the earliest immune response to prenatal transplantation.