CD47 (integrin-associated protein) engagement of dendritic cell and macrophage counterreceptors is required to prevent the clearance of donor lymphohematopoietic cells.

CD47 (integrin-associated protein) engagement of dendritic cell and macrophage counterreceptors is required to prevent the clearance of donor lymphohematopoietic cells.
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DOI:
10.1084/jem.194.4.541
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发表时间:
2001-08-20
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Taylor PA
Taylor PA
中科院分区:
其他
文献类型:
--
作者:
Blazar BR;Lindberg FP;Ingulli E;Panoskaltsis-Mortari A;Oldenborg PA;Iizuka K;Yokoyama WM;Taylor PA

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整合素相关蛋白(CD 47)是一种广泛表达的蛋白质,可共刺激T细胞、促进白细胞迁移并抑制巨噬细胞清除功能。为了确定CD 47在调节同种异体反应中的作用,将CD 47 +/+或CD 47 −/− T细胞输注到辐射或非条件性主要组织相容性复合体的不同受体中。CD 47 −/− T细胞显著降低了移植物抗宿主病致死率。供体CD 47 −/− T细胞未能植入免疫缺陷的同种异体受体。CD 47 −/−骨髓不能重建严重辐射的同种异体或同源免疫缺陷的CD 47 +/+受体。这些数据表明,CD 47 −/− T细胞和骨髓细胞被先天免疫系统清除。为了解决这一假设,在体内输注染料标记的CD 47 −/−和CD 47 +/+淋巴细胞或骨髓细胞,并跟踪清除。染料标记的CD 47 −/−细胞被脾树突状细胞和巨噬细胞吞噬,导致输注后1天内几乎所有CD 47 −/−淋巴造血细胞被清除。宿主吞噬细胞耗尽的CD 47 +/+受体部分接受同种异体CD 47 −/− T细胞。因此,树突状细胞和巨噬细胞清除具有下调的CD 47密度的淋巴造血细胞。CD 47表达可能是决定淋巴造血细胞是否存活或被清除的关键指标。
Integrin-associated protein (CD47) is a broadly expressed protein that costimulates T cells, facilitates leukocyte migration, and inhibits macrophage scavenger function. To determine the role of CD47 in regulating alloresponses, CD47+/+ or CD47−/− T cells were infused into irradiated or nonconditioned major histocompatibility complex disparate recipients. Graft-versus-host disease lethality was markedly reduced with CD47−/− T cells. Donor CD47−/− T cells failed to engraft in immunodeficient allogeneic recipients. CD47−/− marrow was unable to reconstitute heavily irradiated allogeneic or congenic immune–deficient CD47+/+ recipients. These data suggested that CD47−/− T cells and marrow cells were cleared by the innate immune system. To address this hypothesis, dye-labeled CD47−/− and CD47+/+ lymphocytes or marrow cells were infused in vivo and clearance was followed. Dye-labeled CD47−/− cells were engulfed by splenic dendritic cells and macrophages resulting in the clearance of virtually all CD47−/− lymphohematopoietic cells within 1 day after infusion. Host phagocyte-depleted CD47+/+ recipients partially accepted allogeneic CD47−/− T cells. Thus, dendritic cells and macrophages clear lymphohematopoietic cells that have downregulated CD47 density. CD47 expression may be a critical indicator for determining whether lymphohematopoietic cells will survive or be cleared.
DOI: 10.1126/science.274.5288.795
发表时间: 1996-11-01
期刊: SCIENCE
影响因子: 56.9
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期刊: The Journal of experimental medicine
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