Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2002-10-17
pubmed:abstractText
The immunosuppressive drugs, cyclosporine A (CsA), tacrolimus, or sirolimus, were analyzed as single agents and in combination with anti-CD40L monoclonal antibody (mAb) for their effects on alloengraftment in mice conditioned with minimal total body irradiation (TBI). Whereas anti-CD40L mAb facilitated chimerism, neither sirolimus nor CsA resulted in substantial alloengraftment. However, sirolimus was synergistic with anti-CD40L mAb for inducing donor chimerism. Contrary to expectations, CsA, a T-cell receptor (TCR) signaling inhibitor, did not abrogate anti-CD40L mAb-facilitated engraftment but rather increased engraftment in anti-CD40L mAb-treated mice. Although tacrolimus alone or with anti-CD40L mAb resulted in similar levels of donor chimerism, donor T-cell reconstitution was very low in tacrolimus-treated mice. At 1 week after transplantation, CsA decreased thymic numbers more profoundly than sirolimus or tacrolimus in anti-CD40L mAb-treated recipients. In contrast, only sirolimus resulted in a decrease in host splenic T-cell numbers in anti-CD40L mAb-treated recipients. Importantly, sirolimus and anti-CD40L mAb induced profound donor tolerance with 100% acceptance of donor skin grafts placed early after bone marrow transplantation (BMT). In contrast, anti-CD40L mAb alone or in combination with CsA resulted in 12% or less donor skin graft acceptance early (1 month) and 60% or less later (3 months) after BMT. These data have clinical relevance and indicate that immunosuppressive pharmacologic agents enhance anti-CD40L mAb-facilitated alloengraftment and tolerance induction under nonmyeloablative conditioning.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3400-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12384443-Animals, pubmed-meshheading:12384443-Antibodies, Monoclonal, pubmed-meshheading:12384443-Apoptosis, pubmed-meshheading:12384443-Bone Marrow Transplantation, pubmed-meshheading:12384443-CD40 Ligand, pubmed-meshheading:12384443-Calcineurin, pubmed-meshheading:12384443-Cyclosporine, pubmed-meshheading:12384443-Drug Evaluation, Preclinical, pubmed-meshheading:12384443-Drug Synergism, pubmed-meshheading:12384443-Female, pubmed-meshheading:12384443-Graft Survival, pubmed-meshheading:12384443-Graft vs Host Disease, pubmed-meshheading:12384443-Immune Tolerance, pubmed-meshheading:12384443-Immunosuppressive Agents, pubmed-meshheading:12384443-Lymphocyte Count, pubmed-meshheading:12384443-Mice, pubmed-meshheading:12384443-Mice, Inbred BALB C, pubmed-meshheading:12384443-Mice, Inbred C57BL, pubmed-meshheading:12384443-Radiation Chimera, pubmed-meshheading:12384443-Sirolimus, pubmed-meshheading:12384443-Skin Transplantation, pubmed-meshheading:12384443-Specific Pathogen-Free Organisms, pubmed-meshheading:12384443-T-Lymphocyte Subsets, pubmed-meshheading:12384443-Tacrolimus, pubmed-meshheading:12384443-Transplantation, Homologous, pubmed-meshheading:12384443-Transplantation Conditioning, pubmed-meshheading:12384443-Whole-Body Irradiation
pubmed:year
2002
pubmed:articleTitle
Combined effects of calcineurin inhibitors or sirolimus with anti-CD40L mAb on alloengraftment under nonmyeloablative conditions.
pubmed:affiliation
University of Minnesota Cancer Center, Division of Bone Marrow Transplantation, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.