Linked Life Data

17513751

Source:http://linkedlifedata.com/resource/pubmed/id/17513751

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2007-5-21
pubmed:abstractText
The ability of dendritic cells (DC) to regulate Ag-specific immune responses via their influence on T regulatory cells (Treg) may be key to their potential as therapeutic tools or targets for the promotion/restoration of tolerance. In this report, we describe the ability of maturation-resistant, rapamycin (RAPA)-conditioned DC, which are markedly impaired in Foxp3(-) T cell allostimulatory capacity, to favor the stimulation of murine alloantigen-specific CD4(+)CD25(+)Foxp3(+) Treg. This was distinct from control DC, especially following CD40 ligation, which potently expanded non-Treg. RAPA-DC-stimulated Treg were superior alloantigen-specific suppressors of T effector responses compared with those stimulated by control DC. Supporting the ability of RAPA to target effector T and B cells, but permit the proliferation and suppressive function of Treg, an infusion of recipient-derived alloantigen-pulsed RAPA-DC followed by a short postoperative course of low-dose RAPA promoted indefinite (>100 day) heart graft survival. This was associated with graft infiltration by CD4(+)Foxp3(+) Treg and the absence of transplant vasculopathy. The adoptive transfer of CD4(+) T cells from animals with long-surviving grafts conferred resistance to rejection. These novel findings demonstrate that, whereas maturation resistance does not impair the capacity of RAPA-DC to modulate Treg, it profoundly impairs their ability to expand T effector cells. A demonstration of this mechanism endorses their potential as tolerance-promoting cellular vaccines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
178
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7018-31
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17513751-Animals, pubmed-meshheading:17513751-Bone Marrow Cells, pubmed-meshheading:17513751-CD4-Positive T-Lymphocytes, pubmed-meshheading:17513751-Dendritic Cells, pubmed-meshheading:17513751-Down-Regulation, pubmed-meshheading:17513751-Epitopes, T-Lymphocyte, pubmed-meshheading:17513751-Forkhead Transcription Factors, pubmed-meshheading:17513751-Heart Transplantation, pubmed-meshheading:17513751-Histocompatibility Antigens Class II, pubmed-meshheading:17513751-Immunosuppressive Agents, pubmed-meshheading:17513751-Isoantigens, pubmed-meshheading:17513751-Lymphocyte Activation, pubmed-meshheading:17513751-Male, pubmed-meshheading:17513751-Mice, pubmed-meshheading:17513751-Mice, Inbred BALB C, pubmed-meshheading:17513751-Mice, Inbred C3H, pubmed-meshheading:17513751-Mice, Inbred C57BL, pubmed-meshheading:17513751-Sirolimus, pubmed-meshheading:17513751-T-Lymphocytes, Regulatory, pubmed-meshheading:17513751-Transplantation Tolerance, pubmed-meshheading:17513751-Up-Regulation
pubmed:year
2007
pubmed:articleTitle
Rapamycin-conditioned dendritic cells are poor stimulators of allogeneic CD4+ T cells, but enrich for antigen-specific Foxp3+ T regulatory cells and promote organ transplant tolerance.
pubmed:affiliation
Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural