Linked Life Data

16210615

Source:http://linkedlifedata.com/resource/pubmed/id/16210615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-10-7
pubmed:abstractText
Developing thymocytes undergo maturation while migrating through the thymus and ultimately emigrate from the organ to populate peripheral lymphoid tissues. The process of thymic emigration is controlled in part via receptor-ligand interactions between the chemokine stromal-derived factor (SDF)-1, and its cognate receptor CXCR4, and sphingosine 1-phosphate (S1P) and its receptor S1PR. The precise mechanism by which S1P/S1PR and CXCR4/SDF-1 contribute to thymic emigration remains unclear. We proposed that S1P-dependent and -independent mechanisms might coexist and involve both S1P-induced chemoattraction and SDF-1-mediated chemorepulsion or fugetaxis of mature thymocytes. We examined thymocyte emigration in thymi from CXCR4-deficient C57BL/6 embryos in a modified assay, which allows the collection of CD62L(high) and CD69(low) recent thymic emigrants. We demonstrated that single-positive (SP) CD4 thymocytes, with the characteristics of recent thymic emigrants, failed to move away from CXCR4-deficient fetal thymus in vitro. We found that the defect in SP CD4 cell emigration that occurred in the absence of CXCR4 signaling was only partially overcome by the addition of the extrathymic chemoattractant S1P and was not associated with abnormalities in thymocyte maturation and proliferative capacity or integrin expression. Blockade of the CXCR4 receptor in normal thymocytes by AMD3100 led to the retention of mature T cells in the thymus in vitro and in vivo. The addition of extrathymic SDF-1 inhibited emigration of wild-type SP cells out of the thymus by nullifying the chemokine gradient. SDF-1 was also shown to elicit a CXCR4-dependent chemorepellent response from fetal SP thymocytes. These novel findings support the thesis that the CXCR4-mediated chemorepellent activity of intrathymic SDF-1 contributes to SP thymocyte egress from the fetal thymus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5115-25
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16210615-Animals, pubmed-meshheading:16210615-CD4-Positive T-Lymphocytes, pubmed-meshheading:16210615-Cell Proliferation, pubmed-meshheading:16210615-Chemokine CXCL12, pubmed-meshheading:16210615-Chemokines, CXC, pubmed-meshheading:16210615-Chemotaxis, Leukocyte, pubmed-meshheading:16210615-Fetus, pubmed-meshheading:16210615-Heterocyclic Compounds, pubmed-meshheading:16210615-Immunophenotyping, pubmed-meshheading:16210615-Integrins, pubmed-meshheading:16210615-Mice, pubmed-meshheading:16210615-Mice, Inbred C57BL, pubmed-meshheading:16210615-Mice, Knockout, pubmed-meshheading:16210615-Organ Culture Techniques, pubmed-meshheading:16210615-Pertussis Toxin, pubmed-meshheading:16210615-Receptors, CXCR4, pubmed-meshheading:16210615-Signal Transduction, pubmed-meshheading:16210615-Thymus Gland
pubmed:year
2005
pubmed:articleTitle
A CXCR4-dependent chemorepellent signal contributes to the emigration of mature single-positive CD4 cells from the fetal thymus.
pubmed:affiliation
Partners AIDS Research Center, Infectious Diseases Medicine, and Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural