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CVI Accepts, published online ahead of print on 7 November 2007
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Clin. Vaccine Immunol. doi:10.1128/CVI.00309-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Characterization of Plasmacytoid Dendritic Cells in Bone Marrow of Pig-tailed Macaques

R. Keith Reeves and Patricia N. Fultz*

Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294

* To whom correspondence should be addressed. Email: pnf{at}uab.edu.


   Abstract

Plasmacytoid dendritic cells (pDCs), one of two types of bone marrow (BM)-derived blood DCs, play an important role in linking innate and adaptive immune responses. Little is known, however, about the nature of pDCs that reside in the BM. Because the SIV-macaque model closely mimics HIV disease in humans, with both infections inducing a decrease in pDCs, we characterized and compared pDCs in the BM with those in peripheral blood (PB) of normal pig-tailed macaques. The results revealed that pDCs from both compartments had the same CD123++HLA-DR+Lin- phenotype and were similar in size. Although BM-pDCs were threefold greater in frequency and tenfold greater in number, they had lower cell-surface expression of both HLA-DR and the costimulatory molecule CD86 than did PB-pDCs. Both BM- and PB-pDCs responded ex vivo to synthetic CpG oligodeoxynucleotides and inactivated influenza virus by upregulating HLA-DR and CD86 and secreting cytokines; however, stimulated BM-pDCs secreted less IFN-{alpha} and TNF-{alpha} per cell than did PB-pDCs. These results suggest that, while BM-pDCs appear phenotypically less mature than PB-pDCs, they do respond to pathogens. Thus, during acute infections these cells could initiate immune responses either in the BM or after rapidly migrating from the BM into the periphery. A better characterization of pDCs in blood and tissues will be beneficial for future studies in macaques that focus on either pathogenesis or vaccine development.







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