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利用器官捐献者进行人类免疫学研究:临床变异对组织和循环中免疫参数的影响。

Human immunology studies using organ donors: Impact of clinical variations on immune parameters in tissues and circulation.

机构信息

Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA.

Department of Surgery, Columbia University Medical Center, New York, NY, USA.

出版信息

Am J Transplant. 2018 Jan;18(1):74-88. doi: 10.1111/ajt.14434. Epub 2017 Sep 8.

Abstract

Organ donors are sources of physiologically healthy organs and tissues for life-saving transplantation, and have been recently used for human immunology studies which are typically confined to the sampling of peripheral blood. Donors comprise a diverse population with different causes of death and clinical outcomes during hospitalization, and the effects of such variations on immune parameters in blood and tissues are not known. We present here a coordinate analysis of innate and adaptive immune components in blood, lymphoid (bone marrow, spleen, lymph nodes), and mucosal (lungs, intestines) sites from a population of brain-dead organ donors (2 months-93 years; n = 291) across eight clinical parameters. Overall, the blood of donors exhibited similar monocyte and lymphocyte content and low serum levels of pro-inflammatory cytokines as healthy controls; however, donor blood had increased neutrophils and serum levels of IL-8, IL-6, and MCP-1 which varied with cause of death. In tissues, the frequency and composition of monocytes, neutrophils, B lymphocytes and T cell subsets in lymphoid or mucosal sites did not vary with clinical state, and was similar in donors independent of the extent of clinical complications. Our results reveal that organ donors maintain tissue homeostasis, and are a valuable resource for fundamental studies in human immunology.

摘要

器官捐献者是用于拯救生命的移植的生理上健康的器官和组织的来源,并且最近已被用于通常仅限于外周血采样的人类免疫学研究。捐献者来自具有不同死亡原因和住院期间临床结果的多样化人群,而这种变化对血液和组织中免疫参数的影响尚不清楚。在这里,我们介绍了对脑死亡器官捐献者(2 个月至 93 岁;n=291)的八个临床参数的血液、淋巴样(骨髓、脾脏、淋巴结)和黏膜(肺、肠)部位的固有和适应性免疫成分的协调分析。总体而言,与健康对照相比,供体血液中的单核细胞和淋巴细胞含量相似,并且血清中促炎细胞因子水平较低;但是,供体血液中的中性粒细胞和血清中白细胞介素 8(IL-8)、白细胞介素 6(IL-6)和单核细胞趋化蛋白 1(MCP-1)水平升高,且其变化与死亡原因有关。在组织中,淋巴样或黏膜部位的单核细胞、中性粒细胞、B 淋巴细胞和 T 细胞亚群的频率和组成不受临床状态的影响,并且在独立于临床并发症程度的供体中相似。我们的结果表明,器官捐献者维持组织内稳态,是人类免疫学基础研究的宝贵资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e14/5740015/84a5bd6dc4ed/nihms894033f1.jpg

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