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Allogeneic reconstitution after nonmyeloablative conditioning: mitigation of graft-versus-host and host-versus-graft reactivity by anti-CD44v6
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 56949
Author(s) Christ, Oliver; Günthert, Ursula; Schmidt, Dirk-Steffen; Zöller, Margot
Author(s) at UniBasel Günthert, Ursula
Year 2002
Title Allogeneic reconstitution after nonmyeloablative conditioning: mitigation of graft-versus-host and host-versus-graft reactivity by anti-CD44v6
Journal Journal of leukocyte biology
Volume 71
Number 1
Pages / Article-Number 33-46
Keywords hematopoiesis, rodent, adhesion molecules, knockout, T lymphocytes
Abstract T-cell maturation is accelerated in transgenic mice expressing rat CD44v4-v7 on T cells, the effect being blocked by anti-CD44v6. This finding suggested functional activity of CD44v6 in thymocyte development. We tested the hypothesis by antibody blocking and using mice with targeted deletion of CD44v6/v7 exon products (CD44v6/v7(-/-)). When lethally irradiated CD44v6/v7-competent (CD44v6/v7(+/+)) mice were reconstituted syngeneically, higher numbers of CD44v6/v7(-/-) than CD44v6/v7(+/+) BMC were required for survival, the period of reconstitution was prolonged, and regain of immunocompetence was delayed. Similar findings were observed in lethally irradiated, anti-CD44v6-treated syngeneic CD44v6/v7(+/+) hosts. Thus, CD44v6/v7 supports maturation and expansion of hematopoietic progenitor cells. Surprisingly, reconstitution with CD44v6/v7(-/-) BMC or anti-CD44v6 treatment of the nonlethally irradiated allogeneic CD44v6/v7(+/+) host had only a minor impact on survival rates. When nonlethally irradiated CD44v6/v7(-/-) hosts received an allogeneic graft, survival rates were improved. These phenomena have been a result of reduced GvH reactivities when the donor was CD44v6/v7(-/-) and reduced HvG reactivities in the CD44v6/v7(-/-) host. Thus, although a deficit or blockade of CD44v6/v7 has a negative impact on hematopoietic reconstitution, a transient blockade will be of benefit for the allogeneically reconstituted host because of a strong reduction in GvH and HvG reactivities.
Publisher Society for Leukocyte Biology
ISSN/ISBN 0741-5400
edoc-URL http://edoc.unibas.ch/dok/A5249205
Full Text on edoc Restricted
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/11781378
ISI-Number WOS:000173191600004
Document type (ISI) Journal Article
 
   

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