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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2872-2879. Prepublished online as a Blood First Edition Paper on June 21, 2007; DOI 10.1182/blood-2006-10-050583. This Article Full Text (PDF) All Versions of this Article: blood-2006-10-050583v1 110/8/2872    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Li, G. Articles by Broxmeyer, H. E. Search for Related Content PubMed PubMed Citation Articles by Li, G. Articles by Broxmeyer, H. E. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 4, 2006 Accepted June 5, 2007 TGF-1 combined with M-CSF and IL-4 induces generation of immune inhibitory cord blood dendritic cells capable of enhancing cytokine-induced ex-vivo expansion of myeloid progenitors Geling Li, Saeid Abediankenari, Young-June Kim, Timothy B. Campbell, Shigeki Ito, Barbara Graham-Evans, Scott Cooper, and Hal E. Broxmeyer* Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN, United States Walther Cancer Institute, Indianapolis, IN, United States * Corresponding author; email: hbroxmey{at}iupui.edu. Tolerogenic dendritic cells (DC) may be valuable in transplantation for silencing immune reaction. M-CSF/IL-4 induces differentiation of cord blood (CB) monocytes into DC (M-DC) with tolerogenic phenotype/function. We assessed whether factors produced by tolerogenic DC could modulate hematopoiesis. TGF-1 added to CB M-DC cultures induced bona fide DC morphology (TGF-M-DC), similar to that of DC generated with TGF- and GM-CSF/IL-4 (TGF-GM-DC). Of conditioned medium (CM) produced from TGF-M-DC, TGF-GM-DC, M-DC, and GM-DC, TGF-M-DC CM was the only one that enhanced SCF, Flt3 ligand and TPO expansion of myeloid progenitor cells ex vivo. This effect was blocked by neutralizing anti-M-CSF Ab, but protein analysis of CM suggested that M-CSF alone was not manifesting enhanced expansion of myeloid progenitors. LPS-stimulated TGF-M-DC induced T cell tolerance/anergy as effectively as M-DC. TGF-M-DC secreted significantly lower concentrations of progenitor cell inhibitory cytokines and were less potent in activating T cells than TGF-GM-DC. Functional differences between TGF-M-DC and TGF-GM-DC included enhanced responses to LPS-induced ERK, JNK, and P38 activation in TGF-M-DC and their immune suppressive-skewed cytokine release profiles. TGF-M-DC appear unique amongst culture generated DC in their capability for silencing immunity while promoting expansion of myeloid progenitors, events that may be of therapeutic value. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Dendritic cells reach out in different directions David M. Bodine Blood 2007 110: 2783. [Full Text] [PDF] This article has been cited by other articles: R. D. Stout, S. K. Watkins, and J. Suttles Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages J. Leukoc. Biol., November 1, 2009; 86(5): 1105 - 1109. [Abstract] [Full Text] [PDF]

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