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

B. R. Blazar, F. P. Lindberg, E. Ingulli, A. Panoskaltsis-Mortari, P. A. Oldenborg, K. Iizuka, W. M. Yokoyama, P. A. Taylor

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)541-549
Number of pages9
JournalJournal of Experimental Medicine
Volume194
Issue number4
DOIs
StatePublished - Aug 20 2001

Keywords

  • Immune tolerance
  • In vivo animal models
  • Stem cells
  • T cells
  • Transplantation

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