Plasmacytoid dendritic cells (pDCs) play an important primary role for antiviral innate immunity by rapidly producing large amounts of type 1 interferon (IFN) upon viral infection. To study pDC biology, we generated a monoclonal antibody, termed 2E6, that recognizes pDCs. Molecular cloning of a cDNA encoding the 2E6 antigen revealed that it is a type II C-type lectin, Ly49Q, that consists of 247 amino acids with high homology to the natural killer (NK) receptor family Ly49, with an immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic domain. Ly49Q is expressed on pDCs but not on NK cells or myeloid dendritic cells. B220+, CD11c+, CD11b- pDCs in bone marrow were divided into Ly49Q+ and Ly49Q- subsets. While both subsets produced IFN-alpha upon cytosine-phosphate-guanosine (CpG) and herpes simplex virus stimulation, Ly49Q- pDCs responded poorly to influenza virus. In addition, Ly49Q- pDCs produced inflammatory cytokines such as interleukin 6 (IL-6), IL-12, and tumor necrosis factor alpha (TNF-alpha) upon stimulation at lower levels than those produced by Ly49Q+ pDCs. In contrast to bone marrow, Ly49Q+ pDCs were only found in peripheral blood, lymph nodes, and spleen. These results indicate that Ly49Q is a specific marker for peripheral pDCs and that expression of Ly49Q defines 2 subsets of pDCs in bone marrow.

Plasmacytoid dendritic cells (pDCs) link innate to acquired immune responses by producing high levels of type I IFN upon infection. In order to identify the specific genes that control pDC, we compared serial analysis of gene expression libraries from human pDCs, herpes simplex virus-stimulated pDCs and monocytes. We found that Ig-like transcript ILT7 is specifically expressed on pDC cell surfaces and is down-regulated when pDC mature in response to viral or bacterial stimulation. ILT7 expression on the cell surface required association with the Fc epsilon RI gamma adaptor molecule. Although treatment with one anti-ILT7-specific mAb suppressed type I IFN production in response to cytosine-phosphate-guanosice (CpG) stimulation, another anti-ILT7 mAb up-regulated type I IFN production. We conclude that ILT7 is a key regulator of human pDC function.

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Background and aimsThe prevalence of Helicobacter pylori (H. pylori) tends to be lower in Western countries such as central Europe compared with Asia. The virulence of H. pylori is influenced by its subtype composition, most importantly by the presence or absence of different types of cytotoxin-associated gene A(CagA). This study aimed to assess the prevalence of H. pylori and its respective CagA phenotype in a large retrospective cohort of patients with gastric cancer or duodenal ulcer at a Western tertiary referral institution.MethodsH. pylori positive gastric biopsy samples from patients diagnosed with the afore mentioned diseases within the past 25 years were re-evaluated by histology for H. pylori and status of gastritis. Confirmed H. pylori positive cases were processed for immunohistochemistry (IHC) for H. pylori,CagA, and EastAsiantype CagA.ResultsThe prevalence of H. pylori positive gastric biopsy samples decreased from 20.7% to 2.3% within the study period. Among the gastric cancer patients, the H. pylori positive rate was 16.6%, and didn’t show significant changes over time (p = 0.38). Contrary, the H. pylori positive rate of duodenal ulcer decreased significantlyfrom 40% to 5% (p = 0.01). Within H. pylori positive groups ofboth diseases, CagA was highly detected at IHC (86% and 78%, respectively). Except for a few patients originating from East Asian countries, all CagA detected in this study were of Western type.ConclusionIn this first Western investigation on the chronological prevalence of H. pylori and its most relevant subtypes, Western type of CagA was highly detected in two important index diseases of the pathogen. This raises further questions about the virulence of this subtype.