Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-8-30
pubmed:abstractText
Flt3 ligand (FL) administration markedly increases bone marrow (BM) stem cells and immature dendritic cells. We investigated the influence of CD40-CD40Ligand (CD154) pathway blockade on antidonor immunity, cytokine production, microchimerism and heart graft survival in BALB/c (H2d) recipients of fully allogeneic C57BL/10 (H2b) FL-mobilized BM (FL-BM) or normal BM. Anti-CD40L mAb strongly suppressed anti-donor T-cell proliferative responses in recipients of either normal or FL-BM, but was less efficient in inhibiting antidonor cytolytic T-cell (CTL) activity, especially in recipients of FL-BM. Interestingly, CD40L blockade was more effective in recipients of multiple compared with single donor BM infusions. Anti-donor cytokine responses revealed complete impairment of IFN-gamma, IL-4 and IL-10 production in recipients of normal BM and CD40L mAb. By contrast, and in agreement with the CTL data, mice given FL-BM retained ability to produce IFN-gamma CD40-CD40L blockade did not promote microchimerism, as evidenced by immunohistology and real time polymerase chain reaction. Nevertheless, anti-CD40L mAb enhanced heart allograft survival in recipients of FL-BM, but the effect was inferior to that achieved with normal BM. These data provide insight into the influence of growth factor-expanded donor BM and costimulation blockade on antidonor immune reactivity and transplant outcome. The comparatively poor outcome obtained using FL-BM plus anti-CD40L mAb in this model may be ascribed to the failure of effectively interdicting antidonor CTL activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1600-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
609-17
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12201361-Animals, pubmed-meshheading:12201361-Bone Marrow Transplantation, pubmed-meshheading:12201361-CD40 Ligand, pubmed-meshheading:12201361-Flow Cytometry, pubmed-meshheading:12201361-Graft Survival, pubmed-meshheading:12201361-Heart Transplantation, pubmed-meshheading:12201361-Immunosuppression, pubmed-meshheading:12201361-Ligands, pubmed-meshheading:12201361-Lymphocyte Culture Test, Mixed, pubmed-meshheading:12201361-Membrane Proteins, pubmed-meshheading:12201361-Mice, pubmed-meshheading:12201361-Mice, Inbred BALB C, pubmed-meshheading:12201361-Mice, Inbred C3H, pubmed-meshheading:12201361-Mice, Inbred C57BL, pubmed-meshheading:12201361-Polymerase Chain Reaction, pubmed-meshheading:12201361-T-Lymphocytes, pubmed-meshheading:12201361-Time Factors, pubmed-meshheading:12201361-Transplantation, Homologous
pubmed:year
2002
pubmed:articleTitle
Normal donor bone marrow is superior to Flt3 ligand-mobilized bone marrow in prolonging heart allograft survival when combined with anti-CD40L (CD154).
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't