DOI: 10.2337/db08-0356
Plasmacytoid precursor dendritic cells from NOD mice exhibit impaired function: are they a component of diabetes pathogenesis?1Institute for Cellular Therapeutics, University of Louisville, University of Louisville, Louisville, KY Objective: Plasmacytoid precursor dendritic cell facilitating cells (p-preDC FC) play a critical role in facilitation of syngeneic and allogeneic hematopoietic stem cells (HSC) engraftment. Here, we evaluated the phenotype and function of CD8+/TCR– FC from NOD mice. Resesrch Design And Methods: The phenotype of CD8+/TCR–FC were analyzed by flow cytometry using sorted FC from NOD, NOR, or B6 mice. The function of NOD FC 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 FC are functionally impaired. They fail to facilitate engraftment of syngeneic and allogeneic HSC in vivo and do not enhance HSC clonogenicity in vitro. NOD FC contain subpopulations similar to those previously described in B6 FC, 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 FC compared to disease-resistant controls. Removal of the CD19+ or NK1.1+DX5+ subpopulations from FC did not significantly affect facilitation. Notably, FL treatment of NOD donors expanded FC total in peripheral blood and restored facilitating function in vivo. Conclusions: These data demonstrate that NOD FC exhibit significantly impaired function that is reversible, since FL restored production of functional FC in NOD mice and suggest that FL plays an important role in the regulation and development of FC function. FC may therefore be linked to diabetes pathogenesis and prevention.
Correspondence: suzanne.ildstad{at}louisville.edu
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