The Journal of Experimental Medicine
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Published online 20 August 2001. doi:10.1084/jem.194.4.541
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© The Rockefeller University Press, 0022-1007/2001/8/541/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 4, August 20, 2001 541-550

Brief Definitive Report

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

Bruce R. Blazara, Frederik P. Lindbergc, Elizabeth Ingullib, Angela Panoskaltsis-Mortaria, Per-Arne Oldenborgc, Koho Iizukad, Wayne M. Yokoyamad, and Patricia A. Taylora

a University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation
b Nephrology Division, Minneapolis, MN 55455
c University of Washington School of Medicine, Department of Medicine, Infectious Diseases Division, Seattle, WA 98195
d Rheumatology Division and Howard Hughes Medical Institute, St. Louis, MO 63110
MMC 109, University of Minnesota Hospital, 420 SE Delaware St., Minneapolis, MN 55416.612-624-3913612-626-2734

blaza001{at}tc.umn.edu

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.

Key Words: transplantation • in vivo animal models • T cells • stem cells • immune tolerance

B.R. Blazar and F.P. Lindberg contributed equally to this work.

P.-A. Oldenborg's present address is Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University SE-901 87, Umeå, Sweden.

© 2001 The Rockefeller University Press


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