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The Journal of Immunology, 2006, 177: 6115-6121.
Copyright © 2006 by The American Association of Immunologists, Inc.

Plasmacytoid Dendritic Cells Do Not Migrate in Intestinal or Hepatic Lymph

Ulf Yrlid*, Vuk Cerovic{dagger}, Simon Milling*, Christopher D. Jenkins*, Jiquan Zhang{ddagger}, Paul R. Crocker{ddagger}, Linda S. Klavinskis{dagger} and G. Gordon MacPherson1,*

* Sir William Dunn School of Pathology, Oxford, United Kingdom; {dagger} Kings College London, Peter Gorer Department of Immunobiology, London, United Kingdom; and {ddagger} Division of Cell Biology and Immunology, Wellcome Trust Biocentre, University of Dundee, Dundee, United Kingdom

Plasmacytoid dendritic cells (pDCs) recognize pathogen-associated molecules, particularly viral, and represent an important mechanism in innate defense. They may however, also have roles in steady-state tolerogenic responses at mucosal sites. pDCs can be isolated from blood, mucosa, and lymph nodes (LNs). Although pDCs can express peripherally derived Ags in LNs and at mucosal sites, it is not clear whether pDCs actually migrate from the periphery in lymph or whether LN pDCs acquire Ags by other mechanisms. To determine whether pDCs migrate in lymph, intestine or liver-draining LNs were removed and thoracic duct leukocytes (TDLs) were collected. TDLs expressing MHC-II and CD45R, but not TCR{alpha}beta or CD45RA, were then analyzed. These enriched TDLs neither transcribe type I IFNs nor secrete inflammatory cytokines in response to viral stimuli in vitro or after a TLR7/8 stimulus in vivo. In addition, these TDLs do not express CD5, CD90, CD200, or Siglec-H, but do express Ig, and therefore represent B cells, despite their lack of CD45RA expression. Intestinal and hepatic lymph are hence devoid of bona fide pDCs under both steady-state conditions and after TLR7/8 stimulation. This shows that any role for pDCs in Ag-specific T cell activation or tolerance must differ from the roles of classical dendritic cells, because it cannot result from peripheral Ag capture, followed by migration of pDCs via lymph to the LN.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Address correspondence and reprint requests to Dr. G. Gordon MacPherson, Sir William Dunn School of Pathology, South Parks Road, Oxford, OX1 3RE, U.K. E-mail address: gordon.macpherson{at}path.ox.ac.uk

2 Abbreviations used in this paper: pDC, plasmacytoid DC; CoeLNX, celiac lymphadenectomy; CpG-ODN, oligonucleotide containing CpG motifs; DC, dendritic cell; DLN, draining lymph node; iL-DC, intestinal lymph DC; L-DC, lymph DC; LN, lymph node; MLNX, mesenteric lymphadenectomy; R-848, Resiquimod; TDL, thoracic duct leukocyte; int, intermediate.




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