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脐带血抗原呈递细胞亚群的选择性发育缺陷。

Selective developmental defects of cord blood antigen-presenting cell subsets.

作者信息

Drohan Laura, Harding James J, Holm Bari, Cordoba-Tongson Eileen, Dekker Cornelia L, Holmes Tyson, Maecker Holden, Mellins Elizabeth D

机构信息

Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5164, USA.

出版信息

Hum Immunol. 2004 Nov;65(11):1356-69. doi: 10.1016/j.humimm.2004.09.011.

Abstract

Defective antigen-presenting cell (APC) function has been hypothesized to contribute to increased infection susceptibility in newborns. We used multiparameter flow cytometry to characterize APC subsets in adult peripheral blood (APB) and cord blood (CB). APB had a higher proportion of CD11c+ dendritic cells (DC), whereas CB mainly contained CD123+ DC. APB was enriched in CD16+CD11c+ DC subset, whereas CD34+CD11c-CD123lo cells were prominent in CB. Lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production was dampened in myeloid DC and monocytes from CB, whereas IL-1alpha production was not different. The reduction in TNF-alpha response did not appear to result from reduced surface detection of LPS, because CD14, toll-like receptor (TLR)-4 and TLR-2 levels were not reduced in CB APC compared with APB cells. Also, there was no correlation between TLR-2 or TLR-4 levels and TNF-alpha production in myeloid DC and monocytes. CB monocytes had lower surface HLA-DR immediately ex vivo. Both APB and CB monocytes upregulated HLA-DR after incubation, but an additional LPS-induced increase in HLA-DR was suggested only in APB monocytes. APB monocytes also showed a greater LPS-induced increase in CD40 expression. Together, our data show significant, selective differences in circulating APC between neonates and adults.

摘要

抗原呈递细胞(APC)功能缺陷被认为是导致新生儿感染易感性增加的原因之一。我们采用多参数流式细胞术对成人外周血(APB)和脐血(CB)中的APC亚群进行了表征。APB中CD11c⁺树突状细胞(DC)比例较高,而CB中主要含有CD123⁺DC。APB富含CD16⁺CD11c⁺DC亚群,而CD34⁺CD11c⁻CD123lo细胞在CB中较为突出。脂多糖(LPS)诱导的肿瘤坏死因子(TNF)-α产生在CB的髓样DC和单核细胞中受到抑制,而白细胞介素-1α的产生没有差异。TNF-α反应的降低似乎不是由于LPS表面检测减少所致,因为与APB细胞相比,CB APC中的CD14、Toll样受体(TLR)-4和TLR-2水平并未降低。此外,髓样DC和单核细胞中TLR-2或TLR-4水平与TNF-α产生之间没有相关性。CB单核细胞在离体时表面HLA-DR水平较低。APB和CB单核细胞在孵育后均上调了HLA-DR,但仅APB单核细胞中LPS诱导的HLA-DR有额外增加。APB单核细胞还显示出LPS诱导的CD40表达增加更为明显。总之,我们的数据显示新生儿和成人循环APC之间存在显著的选择性差异。

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