Linked Life Data

14970938

Source:http://linkedlifedata.com/resource/pubmed/id/14970938

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-2-18
pubmed:abstractText
Allogeneic reduced-intensity stem cell transplantation (RISCT) decreases regimen-associated morbidity and mortality, but it is unfortunately still constrained by the same immune T-cell reactions that limit myeloablative transplantation, including graft rejection, graft-versus-host disease (GVHD), and suboptimal graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effects. Graft rejection is mediated by host T cells, whereas GVHD and GVL/GVT effects are initiated by donor T cells, and to this extent, future advances in RISCT will likely benefit from an ability to modulate both donor and host T-cell immunity. As a step in this direction, we have developed a RISCT approach that first involves chemotherapy-induced host T-cell ablation, and second involves administration of allogeneic inocula enriched for donor CD4(+) Th2 and CD8(+) Tc2 T-cell subsets that in murine studies mediate reduced GVHD. In a pilot clinical trial, "immunoablative" RISCT with human leukocyte antigen (HLA)-matched related allografts resulted in rapid and complete donor chimerism and GVL effects early post-transplant, with GVHD being the primary toxicity. Using this immunoablative RISCT approach, we are now evaluating the feasibility and safety of augmenting allografts with additional donor CD4(+) Th2 cells that are generated in vitro via CD3/CD28 costimulation in the presence of interleukin (IL)-4. We review the biology of host and donor T-cell immunity during allogeneic RISCT and discuss the strategies of host immunoablation and donor Th2 and Tc2 cell therapy as potential means to improve the clinical results in RISCT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0093-7754
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
56-67
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Immunoablative reduced-intensity stem cell transplantation: potential role of donor Th2 and Tc2 cells.
pubmed:affiliation
National Institutes of Health, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Review