title: Plasmacytoid dendritic cells (PDC) are the major DC subset innately producing cytokines in human lymph nodes.
abstract: Plasmacytoid dendritic cells (PDC) constitute a distinct subset of DC found in human peripheral lymph nodes (LN), but little is known about their function. Cell suspensions were prepared from tumor draining LN (n=20) and control LN (n=11) of women undergoing surgical resection for primary breast cancer and elective surgery for benign conditions, respectively. Using four-color flow cytometry, human leukocyte antigen-DR+ DC subsets were identified phenotypically. The proportions and numbers of cells innately producing interleukin (IL)-4, IL-10, IL-12, and interferon-gamma (IFN-gamma) were also measured from intracellular accumulation of cytokine after blocking with monensin. All flow cytometry data were collected without compensation and were compensated off-line using the Winlist algorithm (Verity software). This package also provided the subtraction program to calculate percentage positive cells and intensity of staining. PDC (CD11c-, CD123+) expressed more cytokines than did myeloid DC (CD11c+) or CD1a+ putative "migratory" DC (P<0.001). LN PDC from patients with a good prognosis (px; n=11) demonstrated a relative increase in IL-12 and IFN-gamma expression (median IL-10:IL-12 ratio=0.78 and median IL-4:IFN-gamma ratio=0.7), and PDC from LN draining poor px cancer (n=9) showed a relative increase in IL-10 and IL-4 expression (median IL-10:IL-12 ratio=1.31 and median IL-4:IFN-gamma ratio=2.6). The difference in IL-4:IFN-gamma expression between good and poor px cancer groups was significant (P<0.05). Thus, PDC innately producing cytokines were identified in cell suspensions from human LN, and the character of PDC cytokine secretion may differ between two breast cancer prognostic groups. We speculate that a shift towards PDC IL-10 and IL-4 expression could promote tumor tolerance in LN draining poor px breast cancer.
authors.affiliation: Antigen Presentation Research Group, Faculty of Medicine, Imperial College London, Northwick Park and St. Marks Campus, Harrow, Middlesex, United Kingdom.
authors.forename: Karina
authors.initials: K
authors.lastname: Cox
authors.forename: Margaret
authors.initials: M
authors.lastname: North
authors.forename: Michael
authors.initials: M
authors.lastname: Burke
authors.forename: Hemant
authors.initials: H
authors.lastname: Singhal
authors.forename: Sophie
authors.initials: S
authors.lastname: Renton
authors.forename: Nayef
authors.initials: N
authors.lastname: Aqel
authors.forename: Sabita
authors.initials: S
authors.lastname: Islam
authors.forename: Stella C
authors.initials: SC
authors.lastname: Knight
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000276:immunology* / Q000556:secondary; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D019139:Tumor Escape / Q000276:immunology
chemical_list: D016207:Cytokines; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma