HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix All Versions of this Article: db08-0356v1 57/9/2360    most recent Purchase Article View Shopping Cart 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 Request Permissions Google Scholar Articles by Huang, Y. Articles by Ildstad, S. T. PubMed PubMed Citation Articles by Huang, Y. Articles by Ildstad, S. T. Social Bookmarking                What's this?

Plasmacytoid Precursor Dendritic Cells From NOD Mice Exhibit Impaired Function

Are They a Component of Diabetes Pathogenesis?

From the Institute for Cellular Therapeutics, University of Louisville, Louisville, Kentucky

Corresponding author: Suzanne T. Ildstad, suzanne.ildstad{at}louisville.edu

OBJECTIVE—Plasmacytoid precursor dendritic cell facilitating cells (p-preDC FCs) play a critical role in facilitation of syngeneic and allogeneic hematopoietic stem cell (HSC) engraftment. Here, we evaluated the phenotype and function of CD8⁺/TCR^– FCs from NOD mice.

RESEARCH DESIGN AND METHODS—The phenotype of CD8⁺/TCR^– FCs was analyzed by flow cytometry using sorted FCs from NOD, NOR, or B6 mice. The function of NOD FCs was evaluated by colony-forming cell (CFC) assay in vitro and syngeneic or allogeneic HSC transplantation in vivo.

RESULTS—We report for the first time that NOD FCs are functionally impaired. They fail to facilitate engraftment of syngeneic and allogeneic HSCs in vivo and do not enhance HSC clonogenicity in vitro. NOD FCs contain subpopulations similar to those previously described in B6 FCs, including p-preDC, CD19⁺, NK1.1⁺DX5⁺, and myeloid cells. However, the CD19⁺ and NK1.1⁺DX5⁺ subpopulations are significantly decreased in number in NOD FCs compared with disease-resistant controls. Removal of the CD19⁺ or NK1.1⁺DX5⁺ subpopulations from FCs did not significantly affect facilitation. Notably, Flt3 ligand (FL) treatment of NOD donors expanded FC total in peripheral blood and restored facilitating function in vivo.

CONCLUSIONS—These data demonstrate that NOD FCs exhibit significantly impaired function that is reversible, since FL restored production of functional FCs in NOD mice and suggest that FL plays an important role in the regulation and development of FC function. FCs may therefore be linked to diabetes pathogenesis and prevention.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?