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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-1-19
pubmed:abstractText
Eliminating alloreactive cells from T-cell populations would enable the transfer of immune function to patients who receive stem cell transplants. However, high-efficiency depletion has proved difficult to achieve. We sought to develop ex vivo approaches for the maximal depletion of alloreactive CD4(+) T cells. Using a flow cytometric cell sorting approach after mixed lymphocyte reaction (MLR) culture, we have found that sorted CFSE(bright) (5-(and-6)-carboxyfluorescein diacetate succinmidyl ester) (nondivided) and activation antigen-negative cells are markedly depleted of alloreactivity. With HLA-mismatched peripheral blood mononuclear cell (PBMC) stimulators we have consistently attained (90%-95%) depletion of alloreactivity. Importantly, when purified matured monocyte-derived dendritic cells (DCs) are used as stimulators, a 100-fold (99%) reduction in alloreactivity was attained, resulting in abrogation of the secondary MLR. Significantly, the CFSE(bright) CD25(-) cells recovered from these cultures retained general immunoreactivity, including responses to Candida and cytomegalovirus (CMV) antigens. In addition, a CFSE-based approach was tested and found to be sufficient for graft-versus-host disease (GVHD) prevention in vivo, in a major histocompatibility complex (MHC) class II disparate murine model. This efficient approach to selectively deplete mature alloantigen-specific T cells may permit enhanced immune reconstitution without GVHD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1158-65
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14525783-Animals, pubmed-meshheading:14525783-CD4-Positive T-Lymphocytes, pubmed-meshheading:14525783-Cell Separation, pubmed-meshheading:14525783-Dendritic Cells, pubmed-meshheading:14525783-Flow Cytometry, pubmed-meshheading:14525783-Fluoresceins, pubmed-meshheading:14525783-Fluorescent Dyes, pubmed-meshheading:14525783-Graft vs Host Disease, pubmed-meshheading:14525783-HLA Antigens, pubmed-meshheading:14525783-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:14525783-Humans, pubmed-meshheading:14525783-Isoantigens, pubmed-meshheading:14525783-Lymphocyte Culture Test, Mixed, pubmed-meshheading:14525783-Lymphocyte Depletion, pubmed-meshheading:14525783-Mice, pubmed-meshheading:14525783-Mice, Inbred C57BL, pubmed-meshheading:14525783-Succinimides, pubmed-meshheading:14525783-Transplantation, Homologous
pubmed:year
2004
pubmed:articleTitle
Ex vivo depletion of alloreactive cells based on CFSE dye dilution, activation antigen selection, and dendritic cell stimulation.
pubmed:affiliation
Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA. godfr007@umn.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't