Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-10-2
pubmed:abstractText
Graft rejection and graft-versus-host disease are major problems in mismatched marrow transplants along with toxicity from standard myeloablative host treatments. We have established a tolerization model, using 1 Gy irradiation, which reduces stem cell capacity to < 10% of control while causing minimal myelosuppression, donor antigen pre-exposure (spleen cells), CD40-ligand antibody blockade and high levels of marrow (40 x 106 cells), which allows for stable long-term multilineage engraftment in H2-mismatched murine marrow transplants. We now show that the establishment of 'microchimaerism' (0.5-3.8%) sets the stage for macrochimaerism, with subsequent marrow infusions in H2-mismatched mice with CD40-ligand blockade only. Neither irradiation nor spleen cell exposure were necessary. When 40 x 106 bone marrow cells were infused on weeks 0, 12, 14 and 16, blood engraftment was about seven times the single 40 x 106 control. When marrow cells were given on weeks 0, 3, 4, 5 and 6, engraftment at 24 weeks post transplant was 17.9 +/- 1.2%, compared with 2.7 +/- 0.8% for the single 40 x 106 control (P = 0.009). We have shown stable, long-term multilineage chimaerism and established that the schedule of marrow administration, not the total cell dose, is critical for tolerization. This approach indicates that microchimaerism can tolerize for subsequent marrow infusions and produce macrochimaerism. This strategy could be applied in clinical human transplants.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0007-1048
pubmed:author
pubmed:issnType
Print
pubmed:volume
119
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
155-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
H2-mismatched transplantation with repetitive cell infusions and CD40 ligand antibody infusions without myeloablation.
pubmed:affiliation
Department of Research, Roger Williams Medical Center, Providence, and UMass Cancer Center, University of Massachusetts, Worcester, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't