Source:http://linkedlifedata.com/resource/pubmed/id/11903384
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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
2002-3-27
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pubmed:abstractText |
The regulatory benefit of apoptosis (activation-induced cell death, AICD) in T cells may be impacted by immunosuppressive agents. We examined this for mycophenolate mofetil (MMF) compared with cyclosporine (CYA). Peripheral blood leukocytes (PBL) were stimulated by either Staph enterotoxin B (SEB) or by anti-CD3 plus anti-CD28. Cell division analysis (sequential reduction in carboxyflourescein diacetate succinimidyl ester, CFSE) was used to measure proliferation and determine status of different cell generations. Apoptosis was measured by annexin V staining, and FasL expression by anti-FasL antibody staining, of activated cells using flow cytometry. CSA and mycophenolic acid (MPA, the active agent of MMF) were added in titration in 3-day cultures. We found that CSA caused diminution in apoptosis but MPA increased it with SEB stimulation. The CSA effect on apoptosis was present when a more calcineurin-dependent stimulus. anti-CD3+ anti-CD28, was used but the MPA effect was less, producing a decrease only in the undivided cells. To look more directly at the differential effect on calcineurin-dependent AICD gene induction of the two agents, we measured Fas-L expression with anti-CD-3 + CD28 stimulation, and confirmed that CYA caused a major decrement in appearance of Fas-L, whereas MPA caused a converse accumulation of it. This seems to be explained by the block more distal in cell activation, resulting in a build-up of a precursor in the activation pathways. We conclude that MMF treatment may be rationale as an adjunct to calcineurin inhibitor treatment because of its converse effect on T cell regulatory apoptosis.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
0902-0063
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
15 Suppl 6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
36-40
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11903384-Apoptosis,
pubmed-meshheading:11903384-Cell Division,
pubmed-meshheading:11903384-Cells, Cultured,
pubmed-meshheading:11903384-Cyclosporine,
pubmed-meshheading:11903384-Flow Cytometry,
pubmed-meshheading:11903384-Humans,
pubmed-meshheading:11903384-Immunosuppressive Agents,
pubmed-meshheading:11903384-Mycophenolic Acid,
pubmed-meshheading:11903384-T-Lymphocytes
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pubmed:year |
2001
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pubmed:articleTitle |
Positive effect on T-cell regulatory apoptosis by mycophenolate mofetil.
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pubmed:affiliation |
The Johns Hopkins Medical Institutions, and the Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21287-8611, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study
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