Linked Life Data

15505608

Source:http://linkedlifedata.com/resource/pubmed/id/15505608

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-10-26
pubmed:abstractText
Acute graft-versus-host disease, a major obstacle to the overall success of allogeneic hematopoietic stem cell transplantation, is primarily induced by a subset of donor T cells. Most strategies to prevent acute graft-versus-host disease target all T cells regardless of their specificity, and this leads to prolonged posttransplantation immunodeficiency. Selective depletion of alloreactive T cells could spare protective immunity and facilitate engraftment and graft-versus-leukemia effects. Recently described depletion strategies target activation markers such as CD25 that are expressed by alloreactive T cells. However, incomplete depletion may occur when a single surface epitope or pathway of apoptosis is targeted that may not be fully and concurrently expressed among all alloreactive cells. We now report on a novel strategy effective in both cord blood and peripheral blood stem cell alloreactive T cells that simultaneously induces 2 independent pathways of apoptosis after stimulation by recipient dendritic cells or Epstein-Barr virus-transformed B cells. First, we demonstrate that the folate antagonist trimetrexate selectively depletes proliferating alloreactive precursors in vitro in a dose- and time-dependent manner. Similarly, a second agent, denileukin diftitox, kills activated alloreactive T cells expressing CD25. Most importantly, these 2 agents can exert their effects in concert with superior efficacy while sparing resting bystander T cells, which remain available to mount antimicrobial or third-party responses.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1083-8791
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
772-83
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Superior depletion of alloreactive T cells from peripheral blood stem cell and umbilical cord blood grafts by the combined use of trimetrexate and interleukin-2 immunotoxin.
pubmed:affiliation
Department of Pediatrics, Pediatric Stem Cell Transplant Program, Duke University Medical Center, Durham, North Carolina 27705, USA. szabo001@mc.duke.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't