title: Plasmacytoid dendritic cells do not migrate in intestinal or hepatic lymph.
abstract: 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 TCRalphabeta 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.
authors.affiliation: Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom.
authors.forename: Ulf
authors.initials: U
authors.lastname: Yrlid
authors.forename: Vuk
authors.initials: V
authors.lastname: Cerovic
authors.forename: Simon
authors.initials: S
authors.lastname: Milling
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Jenkins
authors.forename: Jiquan
authors.initials: J
authors.lastname: Zhang
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crocker
authors.forename: Linda S
authors.initials: LS
authors.lastname: Klavinskis
authors.forename: G Gordon
authors.initials: GG
authors.lastname: MacPherson
mesh_terms: D000818:Animals; D002465:Cell Movement; D003713:Dendritic Cells / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007093:Imidazoles / Q000494:pharmacology; D007422:Intestines / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D007962:Leukocytes / Q000737:chemistry / Q000276:immunology; D008099:Liver / Q000276:immunology*; D008196:Lymph / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D009975:Orthomyxoviridae; D051381:Rats; D011919:Rats, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013897:Thoracic Duct / Q000276:immunology
chemical_list: C408982:CPG-oligonucleotide; D000949:Histocompatibility Antigens Class II; D007093:Imidazoles; D009838:Oligodeoxyribonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens; C402365:resiquimod