Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2006-9-27
pubmed:abstractText
Studies of mechanisms of disease regulation by CD4+CD25+ regulatory T cells (Treg) have been focused on their interaction with effector T cells; however, the possibility that regulation might involve noncognate cells has not been explored in detail. This study investigated the effect of CD4+CD25+ Treg on macrophage proinflammatory properties and phenotype in vitro and found that they modulate macrophages by inhibiting their activation, leading to reduced proinflammatory cytokine production and a downregulated effector phenotype. For testing the in vivo significance of this effect, CD4+CD25+ T cells that expressed high levels of Foxp3 were reconstituted into SCID mice after induction of Adriamycin nephropathy, a noncognate model of chronic renal disease. CD4+CD25+ T cells significantly reduced glomerular and interstitial injury. In addition, there was a significant fall in the number of macrophages in both the glomeruli and interstitium of SCID mice that were reconstituted with Treg as compared with the Adriamycin alone group. Blockade of TGF-beta using neutralizing antibodies significantly impaired the protective effect of Treg. These findings delineate a TGF-beta-dependent Treg-macrophage inhibitory interaction that can explain cognate-independent protection by Treg.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2731-41
pubmed:meshHeading
pubmed-meshheading:16988067-Animals, pubmed-meshheading:16988067-Antigens, CD4, pubmed-meshheading:16988067-Cytokines, pubmed-meshheading:16988067-Disease Models, Animal, pubmed-meshheading:16988067-Doxorubicin, pubmed-meshheading:16988067-Flow Cytometry, pubmed-meshheading:16988067-Forkhead Transcription Factors, pubmed-meshheading:16988067-Immunoenzyme Techniques, pubmed-meshheading:16988067-Interleukin-2 Receptor alpha Subunit, pubmed-meshheading:16988067-Kidney, pubmed-meshheading:16988067-Kidney Failure, Chronic, pubmed-meshheading:16988067-Macrophages, pubmed-meshheading:16988067-Male, pubmed-meshheading:16988067-Mice, pubmed-meshheading:16988067-Mice, Inbred BALB C, pubmed-meshheading:16988067-Mice, SCID, pubmed-meshheading:16988067-Phenotype, pubmed-meshheading:16988067-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16988067-T-Lymphocytes, Regulatory, pubmed-meshheading:16988067-Transforming Growth Factor beta
pubmed:year
2006
pubmed:articleTitle
CD4+CD25+ regulatory T cells protect against injury in an innate murine model of chronic kidney disease.
pubmed:affiliation
Centre for Transplantation and Renal Research, The University of Sydney at Westmead Millennium Institute, Westmead NSW 2145, Australia. deepika_mahajan@wmi.usyd.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't