Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2011-3-18
pubmed:abstractText
Human hematolymphoid mice have become valuable tools for the study of human hematopoiesis and uniquely human pathogens in vivo. Recent improvements in xenorecipient strains allow for long-term reconstitution with a human immune system. However, certain hematopoietic lineages, for example, the myeloid lineage, are underrepresented, possibly because of the limited cross-reactivity of murine and human cytokines. Therefore, we created a nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor-?-null (NOD-SCID IL2R?(null)) mouse strain that expressed human stem cell factor, granulocyte-macrophage colony-stimulating factor, and interleukin-3, termed NSG-SGM3. Transplantation of CD34(+) human hematopoietic stem cells into NSG-SGM3 mice led to robust human hematopoietic reconstitution in blood, spleen, bone marrow, and liver. Human myeloid cell frequencies, specifically, myeloid dendritic cells, were elevated in the bone marrow of humanized NSG-SGM3 mice compared with nontransgenic NSG recipients. Most significant, however, was the increase in the CD4(+)FoxP3(+) regulatory T-cell population in all compartments analyzed. These CD4(+)FoxP3(+) regulatory T cells were functional, as evidenced by their ability to suppress T-cell proliferation. In conclusion, humanized NSG-SGM3 mice might serve as a useful model to study human regulatory T-cell development in vivo, but this unexpected lineage skewing also highlights the importance of adequate spatiotemporal expression of human cytokines for future xenorecipient strain development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3076-86
pubmed:dateRevised
2011-5-16
pubmed:meshHeading
pubmed-meshheading:21252091-Animals, pubmed-meshheading:21252091-Cell Lineage, pubmed-meshheading:21252091-Cell Proliferation, pubmed-meshheading:21252091-Forkhead Transcription Factors, pubmed-meshheading:21252091-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:21252091-Hematopoiesis, pubmed-meshheading:21252091-Humans, pubmed-meshheading:21252091-Immune System, pubmed-meshheading:21252091-Interleukin Receptor Common gamma Subunit, pubmed-meshheading:21252091-Interleukin-3, pubmed-meshheading:21252091-Mice, pubmed-meshheading:21252091-Mice, Inbred NOD, pubmed-meshheading:21252091-Mice, SCID, pubmed-meshheading:21252091-Mice, Transgenic, pubmed-meshheading:21252091-Phenotype, pubmed-meshheading:21252091-Stem Cell Factor, pubmed-meshheading:21252091-T-Lymphocytes, Regulatory, pubmed-meshheading:21252091-Thymus Gland
pubmed:year
2011
pubmed:articleTitle
Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2R?(null) humanized mice.
pubmed:affiliation
Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural