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粒细胞集落刺激因子动员的外周血单个核细胞来源的CD14+细胞对同种抗原诱导的T细胞增殖的抑制作用。

Suppression of alloantigen-induced T-cell proliferation by CD14+ cells derived from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells.

作者信息

Mielcarek M, Martin P J, Torok-Storb B

机构信息

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.

出版信息

Blood. 1997 Mar 1;89(5):1629-34.

PMID:9057645
Abstract

The proliferative responsiveness of granulocyte colony-stimulating factor (G-CSF)-mobilized blood was studied in uni-directional mixed leukocyte cultures. Unfractionated mononuclear cells from mobilized blood obtained by leukapheresis at day 4 after initiation of G-CSF (G-PBMC) were hyporesponsive (31.5% +/- 9.2% response, P = .003) compared to mononuclear cells obtained from the peripheral blood before administration of G-CSF (preG-PBMC). There was great variability among donors when purified preG- and G-CD4 cells were compared. In eight of 10 donors, G-CD4 cells were equally responsive or moderately hyporesponsive; in two of 10 donors, G-CD4 cells were more strikingly hyporesponsive. CD14 cells derived from leukapheresis products (G-CD14 cells) suppressed alloantigen-induced proliferation by 48.6% +/- 7.5% when added to preG-PBMC or preG-CD4 cells at responder-CD14 ratios of 2:1 (P < .001). Suppression was evident (14.4% +/- 5.0%) even at responder-CD14 ratios of 8:1 and was largely contact-independent. PreG- and G-CD14 cells had equivalent potency in suppressing proliferative responses. Given that G-CSF-mobilized blood cell grafts contain 50-fold more CD14 cells and only 10-fold more T cells than marrow, we propose that suppression of donor T cells by the large proportion of monocytes present in leukapheresis products could contribute to the unexpectedly low incidence and severity of graft-versus-host disease after peripheral blood stem cell transplantation.

摘要

在单向混合白细胞培养中研究了粒细胞集落刺激因子(G-CSF)动员的血液的增殖反应性。与在给予G-CSF之前从外周血获得的单核细胞(preG-PBMC)相比,在开始使用G-CSF后第4天通过白细胞分离术获得的动员血液中的未分离单核细胞(G-PBMC)反应低下(反应率为31.5%±9.2%,P = 0.003)。当比较纯化的preG-和G-CD4细胞时,供体之间存在很大差异。在10名供体中的8名中,G-CD4细胞反应性相同或中度反应低下;在10名供体中的2名中,G-CD4细胞反应性更显著低下。当以应答者-CD14比例为2:1添加到preG-PBMC或preG-CD4细胞中时,来自白细胞分离术产物的CD14细胞(G-CD14细胞)抑制同种异体抗原诱导的增殖达48.6%±7.5%(P < 0.001)。即使在应答者-CD14比例为8:1时抑制也很明显(14.4%±5.0%),并且在很大程度上与接触无关。preG-和G-CD14细胞在抑制增殖反应方面具有同等效力。鉴于G-CSF动员的血细胞移植物中CD14细胞比骨髓多50倍,而T细胞仅多10倍,我们提出白细胞分离术产物中存在的大量单核细胞对供体T细胞的抑制可能导致外周血干细胞移植后移植物抗宿主病的发生率和严重程度出乎意料地低。

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