期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 194, 期 4, 页码 541-549出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.194.4.541
关键词
transplantation; in vivo animal models; T cells; stem cells; immune tolerance
资金
- NHLBI NIH HHS [R01 HL063452, R01 HL055209, R37HL-56067, R01HL63452, R37 HL056067, R01HL55209] Funding Source: Medline
- NIAID NIH HHS [R01AI-34495, R01 AI-33903, R01 AI034495, R01 AI033903, P01AI-35225, R01-AI-34285, K08AI 01503] Funding Source: Medline
- NIGMS NIH HHS [R01GM-57573, R01 GM057573] Funding Source: Medline
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据