Cd47 (Integrin-Associated Protein) Engagement of Dendritic Cell and Macrophage Counterreceptors Is Required to Prevent the Clearance of Donor Lymphohematopoietic Cells

Author:

Blazar Bruce R.1,Lindberg Frederik P.2,Ingulli Elizabeth3,Panoskaltsis-Mortari Angela1,Oldenborg Per-Arne2,Iizuka Koho4,Yokoyama Wayne M.4,Taylor Patricia A.1

Affiliation:

1. University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation

2. University of Washington School of Medicine, Department of Medicine, Infectious Diseases Division, Seattle, WA 98195

3. Nephrology Division, Minneapolis, MN 55455

4. Rheumatology Division and Howard Hughes Medical Institute, St. Louis, MO 63110

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Reference22 articles.

1. Integrin-associated proteina 50-kD plasma membrane antigen physically and functionally associated with integrins;Brown;J. Cell Biol.,1990

2. Cross talk between α(v)β3 and α4β1 integrins regulates lymphocyte migration on vascular cell adhesion molecule 1;Imhof;Eur. J. Immunol.,1997

3. T cell stimulation via CD47agonistic and antagonistic effects of CD47 monoclonal antibody 1/1A4;Waclavicek;J. Immunol.,1997

4. Costimulation of T cell activation by integrin-associated protein (CD47) is an adhesion-dependent, CD28-independent signaling pathway;Reinhold;J. Exp. Med.,1997

5. Integrin-associated protein (CD47) is a comitogenic molecule on CD3-activated human T cells;Ticchioni;J. Immunol.,1997

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3