Linked Life Data

9402687

Source:http://linkedlifedata.com/resource/pubmed/id/9402687

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-1-16
pubmed:abstractText
Repeated administration of monoclonal antibodies (mAb) directed against the CD4 lymphocyte receptor may induce specific, long-lasting unresponsiveness to fully MHC-mismatched cardiac allografts in rats without additional immunosuppression. We assessed the effect of a single dose of murine anti-rat depleting anti-CD4 mAb (OX-38) on allograft survival in high- and low-responder rat strain combinations. Isogenic strains of DA (RT1av1), PVG (RT1c), AUG (RT1c), and WF (RT1u) rats were used. Recipients in antibody treated groups were given one dose of 5 mg/kg OX-38 mAb on the day of transplant, a dose which was shown to effectively deplete (or block) circulating CD4+ T cells. Other groups were treated for 10 days with cyclosporin A (CsA) and/or Linomide, a novel immunomodulator, which is the first compound able to fully eliminate the effect of CsA in the rat cardiac allograft model. The DA strain was identified as a low-responder to the allogeneic haplotype RT1c (PVG or AUG), but not to RT1u (WF), and developed true tolerance following RT1c grafting and OX-38 or low-dose CsA (5 mg/kg) induction, as verified by the response to retransplantation of a graft from the same donor strain or a third-party challenge. PVG recipients of DA grafts were characterized by high response and only modest (OX-38; median 9.5 days) or moderate (CsA; 23.5 days) prolongation of graft survival. Contrasting graft survival results were obtained in the low-responder combination, either very early rejection (at 10 days) or permanent graft survival (> 100 days). Linomide challenge affected CsA treatment in the high-responder combination but not tolerance induction in the low-responder combination, or the effect of OX-38. It was concluded that in rat heart transplantation a single-dose anti-CD4 mAb therapy may induce permanent donor-specific unresponsiveness in a low-responder strain combination, and that anti-CD4 mAb seems to be unique among immunosuppressive agents while being resistent to challenge by Linomide.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0966-3274
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
204-11
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9402687-Adjuvants, Immunologic, pubmed-meshheading:9402687-Animals, pubmed-meshheading:9402687-Antibodies, Monoclonal, pubmed-meshheading:9402687-Antigens, CD4, pubmed-meshheading:9402687-CD4-CD8 Ratio, pubmed-meshheading:9402687-CD4-Positive T-Lymphocytes, pubmed-meshheading:9402687-CD8-Positive T-Lymphocytes, pubmed-meshheading:9402687-Cyclosporine, pubmed-meshheading:9402687-Heart Transplantation, pubmed-meshheading:9402687-Hydroxyquinolines, pubmed-meshheading:9402687-Immunoglobulin G, pubmed-meshheading:9402687-Immunosuppressive Agents, pubmed-meshheading:9402687-Male, pubmed-meshheading:9402687-Mice, pubmed-meshheading:9402687-Rats, pubmed-meshheading:9402687-Rats, Inbred Strains, pubmed-meshheading:9402687-Species Specificity, pubmed-meshheading:9402687-Transplantation, Homologous
pubmed:year
1997
pubmed:articleTitle
Single dose anti-CD4 monoclonal antibody for induction of tolerance to cardiac allograft in high- and low-responder rat strain combinations.
pubmed:affiliation
Department of Experimental Research, Lund University, University Hospital, Malmö, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't