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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-4-5
pubmed:abstractText
We reported that a 60-day course of combination therapy with tacrolimus and sirolimus induced long-term survival of renal allograft after withdrawal of immunosuppressants in Vervet monkeys. In the present study, the mechanism of drug-induced allograft survival was evaluated via Th1/Th2 cytokines, apoptosis and MLC activity in primates. MATERIALS AND METHODS: Cytokines were evaluated by ELISA. MLR and CTL assays were performed by incorporation of 72 hours (3)H-TdR and 4 hours (51)Cr release assay. RESULTS: A 60-day course of tacrolimus with sirolimus resulted in long-term survival of kidney allografts. (67% > 100 days) without intermittent acute rejection. Low sensitivity to MLR was seen in long-term renal allograft survival among monkeys treated with tacrolimus and sirolimus. Increased levels of CD3(+)CD8(+), CD3(+)/CD56(+) NKT cells and CD86(+)CD8(-)CD11(+) dendritic cells were observed. A population of high expression of CD4(+)FasL(+) was detected. In addition, the concentrations of IL-2 and IFN-gamma from long-term allograft surviving monkeys was not significantly increased, rather a late phase dominance of Th2, IL-4, IL-10, and TGF-beta was found correlated with long-term survival of recipients. In conclusion, the mechanism of tacrolimus and sirolimus induced long-term allograft survival in primates relates to up-regulated FasL expression, NKT cells and dendritic cells, with downregulation of MLR sensitivity. It is also associated with late-dominant expression of Th2 cytokines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0041-1345
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
150-4
pubmed:meshHeading
pubmed:articleTitle
Immunological evaluation of combination therapy with tacrolimus and sirolimus on long-term allograft survival in nonhuman primates.
pubmed:affiliation
Laboratory of Experimental Surgery, Research Center of CHUM, Notre-Dame Hospital, University of Montreal, Montreal, Quebec, Canada H2L 2W5.
pubmed:publicationType
Journal Article