Linked Life Data

17785803

Source:http://linkedlifedata.com/resource/pubmed/id/17785803

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-9-5
pubmed:abstractText
Programmed death-ligand (PD-L)1 and PD-L2, newer B7 superfamily members, are implicated in the negative regulation of immune responses and peripheral tolerance. To examine their function in alloimmunity, we used the murine model of orthotopic corneal transplantation. We demonstrate that PD-L1, but not PD-L2, is constitutively expressed at high levels by the corneal epithelial cells, and at low levels by corneal CD45+ cells in the stroma, whereas it is undetectable on stromal fibroblasts and corneal endothelial cells. Inflammation induces PD-L1 up-regulation by corneal epithelial cells, and infiltration of significant numbers of PD-L1+CD45+CD11b+ cells. Blockade with anti-PD-L1 mAb dramatically enhances rejection of C57BL/6 corneal allografts by BALB/c recipients. To examine the selective contribution of donor vs host PD-L1 in modulating allorejection, we used PD-L1-/- mice as hosts or donors of combined MHC and minor H-mismatched corneal grafts. BALB/c grafts placed in PD-L1-/- C57BL/6 hosts resulted in pronounced T cell priming in the draining lymph nodes, and universally underwent rapid rejection. Allografts from PD-L1-/- C57BL/6 donors were also significantly more susceptible to rejection than wild-type C57BL/6 grafts placed into BALB/c hosts, primarily as a result of increased T cell infiltration rather than enhanced priming. Taken together, our results identify differential roles for recipient vs donor PD-L1 in regulating induction vs effector of alloimmunity in corneal grafts, the most common form of tissue transplantation, and highlight the importance of peripheral tissue-derived PD-L1 in down-regulating local immune responses.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
179
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3672-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17785803-Animals, pubmed-meshheading:17785803-Antigens, CD274, pubmed-meshheading:17785803-Antigens, CD45, pubmed-meshheading:17785803-Antigens, CD80, pubmed-meshheading:17785803-Cell Movement, pubmed-meshheading:17785803-Cornea, pubmed-meshheading:17785803-Corneal Transplantation, pubmed-meshheading:17785803-Down-Regulation, pubmed-meshheading:17785803-Graft Enhancement, Immunologic, pubmed-meshheading:17785803-Graft Survival, pubmed-meshheading:17785803-Immune Tolerance, pubmed-meshheading:17785803-Lymphocyte Activation, pubmed-meshheading:17785803-Membrane Glycoproteins, pubmed-meshheading:17785803-Mice, pubmed-meshheading:17785803-Mice, Inbred BALB C, pubmed-meshheading:17785803-Mice, Inbred C57BL, pubmed-meshheading:17785803-Mice, Knockout, pubmed-meshheading:17785803-Peptides, pubmed-meshheading:17785803-T-Lymphocyte Subsets, pubmed-meshheading:17785803-Tissue Donors
pubmed:year
2007
pubmed:articleTitle
The function of donor versus recipient programmed death-ligand 1 in corneal allograft survival.
pubmed:affiliation
Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural