Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1994-10-18
pubmed:abstractText
Graft-versus-host disease (GVHD), a pathological condition associated with BMT, results from activation of donor T lymphocytes by host tissues. CD28 and CTLA-4 are structurally related T cell receptors for members of the B7 (CD80) gene family, which transmit important costimulatory signals for T cell activation in vitro and in vivo. Here we have investigated the effects of CTLA4Ig, a soluble form of CTLA-4, on lethal GVHD in a murine model. Lethal GVHD was induced by transfer of parent C57BL/6 bone marrow and spleen cells into lethally irradiated (C57BL/6 x DBA/2)F1 recipients. Short courses of treatment with CTLA4Ig did not block engraftment, but prolonged survival of BMT recipients even when administration was delayed for 6 days after transplantation. CTLA4Ig-treated survivors of GVHD maintained body weight and did not exhibit visible signs of GVHD. However, treatment regimens that maximally prolonged survival did not detectably prevent T cell-mediated hematological abnormalities associated with GVHD, including pancytopenia and abnormal cellular composition of the spleen. Our data thus show that the lethality of acute GVHD in this model system is more dependent upon CD28/CTLA-4 costimulation than are other GVHD-associated abnormalities, and can be blocked for an extended period by brief treatment with CTLA4Ig.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0041-1337
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
58
pubmed:geneSymbol
B7, CD80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
602-10
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:8091487-Animals, pubmed-meshheading:8091487-Antigens, CD, pubmed-meshheading:8091487-Antigens, CD28, pubmed-meshheading:8091487-Antigens, Differentiation, pubmed-meshheading:8091487-B-Lymphocytes, pubmed-meshheading:8091487-Bone Marrow Transplantation, pubmed-meshheading:8091487-CHO Cells, pubmed-meshheading:8091487-CTLA-4 Antigen, pubmed-meshheading:8091487-Cricetinae, pubmed-meshheading:8091487-Disease Models, Animal, pubmed-meshheading:8091487-Female, pubmed-meshheading:8091487-Graft vs Host Disease, pubmed-meshheading:8091487-Humans, pubmed-meshheading:8091487-Immunoconjugates, pubmed-meshheading:8091487-Major Histocompatibility Complex, pubmed-meshheading:8091487-Mice, pubmed-meshheading:8091487-Mice, Inbred C57BL, pubmed-meshheading:8091487-Signal Transduction, pubmed-meshheading:8091487-T-Lymphocyte Subsets
pubmed:year
1994
pubmed:articleTitle
CTLA4Ig treatment ameliorates the lethality of murine graft-versus-host disease across major histocompatibility complex barriers.
pubmed:affiliation
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
pubmed:publicationType
Journal Article