Linked Life Data

21788504

Source:http://linkedlifedata.com/resource/pubmed/id/21788504

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2011-8-11
pubmed:abstractText
The homeostatic control mechanisms regulating human leukocyte numbers are poorly understood. Here, we assessed the role of phagocytes in this process using human immune system (HIS) BALB/c Rag2(-/-)IL-2R?c(-/-) mice in which human leukocytes are generated from transplanted hematopoietic progenitor cells. Interactions between signal regulatory protein alpha (SIRP?; expressed on phagocytes) and CD47 (expressed on hematopoietic cells) negatively regulate phagocyte activity of macrophages and other phagocytic cells. We previously showed that B cells develop and survive robustly in HIS mice, whereas T and natural killer (NK) cells survive poorly. Because human CD47 does not interact with BALB/c mouse SIRP?, we introduced functional CD47/SIRP? interactions in HIS mice by transducing mouse CD47 into human progenitor cells. Here, we show that this procedure resulted in a dramatic and selective improvement of progenitor cell engraftment and human T- and NK-cell homeostasis in HIS mouse peripheral lymphoid organs. The amount of engrafted human B cells also increased but much less than that of T and NK cells, and total plasma IgM and IgG concentrations increased 68- and 35-fold, respectively. Whereas T cells exhibit an activated/memory phenotype in the absence of functional CD47/SIRP? interactions, human T cells accumulated as CD4(+) or CD8(+) single-positive, naive, resting T cells in the presence of functional CD47/SIRP? interactions. Thus, in addition to signals mediated by T cell receptor (TCR)/MHC and/or IL/IL receptor interactions, sensing of cell surface CD47 expression by phagocyte SIRP? is a critical determinant of T- and NK-cell homeostasis under steady-state conditions in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13224-9
pubmed:meshHeading
pubmed-meshheading:21788504-Animals, pubmed-meshheading:21788504-Antigens, CD47, pubmed-meshheading:21788504-Antigens, Differentiation, pubmed-meshheading:21788504-B-Lymphocytes, pubmed-meshheading:21788504-DNA-Binding Proteins, pubmed-meshheading:21788504-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:21788504-Hematopoietic Stem Cells, pubmed-meshheading:21788504-Homeostasis, pubmed-meshheading:21788504-Humans, pubmed-meshheading:21788504-Interleukin Receptor Common gamma Subunit, pubmed-meshheading:21788504-Killer Cells, Natural, pubmed-meshheading:21788504-Kinetics, pubmed-meshheading:21788504-Lymphopoiesis, pubmed-meshheading:21788504-Mice, pubmed-meshheading:21788504-Mice, Inbred BALB C, pubmed-meshheading:21788504-Mice, Inbred NOD, pubmed-meshheading:21788504-Protein Binding, pubmed-meshheading:21788504-Receptors, Immunologic, pubmed-meshheading:21788504-Receptors, Interleukin-2, pubmed-meshheading:21788504-Spleen, pubmed-meshheading:21788504-Survival Analysis, pubmed-meshheading:21788504-T-Lymphocytes, pubmed-meshheading:21788504-Thymus Gland, pubmed-meshheading:21788504-Transplantation, Heterologous
pubmed:year
2011
pubmed:articleTitle
Functional CD47/signal regulatory protein alpha (SIRP(alpha)) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo.
pubmed:affiliation
Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, Center for Immunology Amsterdam, 1105AZ Amsterdam, The Netherlands. n.legrand@amc.uva.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't