Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-1-3
pubmed:abstractText
The induction and maintenance of allograft tolerance is a daunting challenge. Although combined blockade of CD28 and CD40 ligand (CD40L)-costimulatory pathways prevents allograft rejection in some murine models, this strategy is unable to sustain engraftment in the most immunogenic allograft and strain combinations. By targeting T cell activation signals 1 and 2 with the novel combination of anti-CD45RB and anti-CD40L, we now demonstrate potent enhancement of engraftment in C57BL/6 recipients that are relatively resistant to costimulatory blockade. This combination significantly augments the induction of tolerance to islet allografts and dramatically prolongs primary skin allograft survival. Compared with either agent alone, anti-CD45RB plus anti-CD40L inhibits periislet infiltration by CD8 cells, B cells, and monocytes; inhibits Th1 cytokines; and increases Th2 cytokine expression within the graft. These data indicate that interference with activation signals one and two may provide synergy essential for prolonged engraftment in situations where costimulatory blockade is only partially effective.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
166
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
322-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11123308-Adjuvants, Immunologic, pubmed-meshheading:11123308-Animals, pubmed-meshheading:11123308-Antibodies, Blocking, pubmed-meshheading:11123308-Antibodies, Monoclonal, pubmed-meshheading:11123308-Antigens, CD45, pubmed-meshheading:11123308-B-Lymphocytes, pubmed-meshheading:11123308-CD40 Ligand, pubmed-meshheading:11123308-CD8-Positive T-Lymphocytes, pubmed-meshheading:11123308-Cell Movement, pubmed-meshheading:11123308-Cytokines, pubmed-meshheading:11123308-Drug Therapy, Combination, pubmed-meshheading:11123308-Graft Survival, pubmed-meshheading:11123308-Islets of Langerhans Transplantation, pubmed-meshheading:11123308-Male, pubmed-meshheading:11123308-Mice, pubmed-meshheading:11123308-Mice, Inbred BALB C, pubmed-meshheading:11123308-Mice, Inbred C57BL, pubmed-meshheading:11123308-Models, Immunological, pubmed-meshheading:11123308-Monocytes, pubmed-meshheading:11123308-Protein Isoforms, pubmed-meshheading:11123308-Signal Transduction, pubmed-meshheading:11123308-Skin Transplantation, pubmed-meshheading:11123308-Transplantation Tolerance
pubmed:year
2001
pubmed:articleTitle
Targeting signal 1 through CD45RB synergizes with CD40 ligand blockade and promotes long term engraftment and tolerance in stringent transplant models.
pubmed:affiliation
Department of Internal Medicine, Yale Medical School, New Haven, CT 06520, USA. david.rothstein@yale.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't