Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-7-15
pubmed:abstractText
Graft-versus-host disease (GVHD), due to the presence of recipient-reactive T cells, limits the usefulness of bone marrow transplantation (BMT) and is a major contributor to patient mortality. To prevent GVHD, murine and human T cells were activated by antigen or mitogens and treated with a genetically engineered form of Pseudomonas exotoxin A (PE) directed against the IL-2 receptor. Treatment with the chimeric toxin eliminated alloreactive cytotoxic T lymphocytes (CTL) as determined by cytotoxicity and mixed lymphocyte culture assays. Precursor frequencies of alloreactive cytotoxic T cells and proliferative T cells were reduced up to 100-fold as shown by limiting dilution assays. Flow cytometric analyses revealed that treatment with the chimeric toxin completely eliminated CD25+ cells from the cultures. Toxin treatment had no significant effect on hematopoietic stem and progenitor cells as determined in vitro by colony-forming assays and in vivo by long-term hematopoietic recovery after 950 rad irradiation. Toxin treatment decreased GVHD in transplanted mice to less than 10% (as compared to 88% in untreated controls). Thus, it is possible to prevent life-threatening GVHD after BMT by using a CD25 receptor-directed toxin to eliminate host-reactive T cells from bone marrow grafts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0268-3369
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
137-44
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:10197798-ADP Ribose Transferases, pubmed-meshheading:10197798-Animals, pubmed-meshheading:10197798-Bacterial Toxins, pubmed-meshheading:10197798-Bone Marrow Transplantation, pubmed-meshheading:10197798-Cell Count, pubmed-meshheading:10197798-Exotoxins, pubmed-meshheading:10197798-Female, pubmed-meshheading:10197798-Graft vs Host Disease, pubmed-meshheading:10197798-Humans, pubmed-meshheading:10197798-Isoantibodies, pubmed-meshheading:10197798-Mice, pubmed-meshheading:10197798-Phenotype, pubmed-meshheading:10197798-Pregnancy, pubmed-meshheading:10197798-Pseudomonas aeruginosa, pubmed-meshheading:10197798-Receptors, Interleukin-2, pubmed-meshheading:10197798-Recombinant Proteins, pubmed-meshheading:10197798-Stem Cells, pubmed-meshheading:10197798-T-Lymphocytes, pubmed-meshheading:10197798-Tissue Donors, pubmed-meshheading:10197798-Virulence Factors
pubmed:year
1999
pubmed:articleTitle
Prevention of graft-versus-host disease (GVHD) by elimination of recipient-reactive donor T cells with recombinant toxins that target the interleukin 2 (IL-2) receptor.
pubmed:affiliation
Department Microbiology and Immunology, University of Arizona, Tucson 85721, USA.
pubmed:publicationType
Journal Article