PMID- 12525872 OWN - NLM STAT- MEDLINE DCOM- 20030812 LR - 20041117 IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 11 IP - 2 DP - 2003 Feb TI - Impaired function of antigen-presenting dendritic cells in patients with chronic hepatitis B: localization of HBV DNA and HBV RNA in blood DC by in situ hybridization. PG - 169-74 AB - Antigen-presenting dendritic cells (DCs), which play a major role in the triggering of primary anti viral immune reactions, may also contribute, in some viral models, to the pathogenesis of persistent viral infection. In fact, impaired immune response to hepatitis B virus (HBV)-encoded antigens is seen in patients with chronic hepatitis B (CH-B). The aim of this study was to check the function of DCs in these patients and to investigate the underlying mechanism. DCs were enriched from peripheral blood mononuclear cells by culturing with interleukin (IL)-4 and granulocyte-macrophage colony stimulating factor for 7 days. The stimulatory capacity of DCs were checked in allogenic mixed leukocyte (MLR) reaction. The levels of IL-12 in the culture supernatants were measured by an enzyme-linked immunosorbent assay. HBV DNA and HBV RNA were localized in DCs by polymerase chain reaction (PCR) in situ hybridization and reverse-transcriptase (RT)-PCR in situ hybridization. The stimulatory capacity of DCs in allogenic MLR was significantly lower in patients with CH-B (36321+/-12523 cpm, n=18) compared to that of normal controls (65678+/-11174 cpm, n=18) (p<0.0001). Significantly lower levels of IL-12 were detected in cultures containing DCs from patients with CH-B than normal controls (46.7+/-25.6 versus 122.4+/- 37.1 pg/ml, p<0.0001). In situ hybridization revealed the localization of HBV DNA and HBV RNA in DCs from patients with CH-B. These results indicate that chronic infection by HBV is associated with functional defects of DCs. Localization of HBV DNA and HBV RNA indicates that DCs may constitute an extra hepatic reservoir and possibly of replication of HBV. FAU - Arima, Shouko AU - Arima S AD - Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-Cho, Ehime 791-0295, Japan. FAU - Akbar, S M Fazle AU - Akbar SM FAU - Michitaka, Kojiro AU - Michitaka K FAU - Horiike, Norio AU - Horiike N FAU - Nuriya, Hideko AU - Nuriya H FAU - Kohara, Michinori AU - Kohara M FAU - Onji, Morikazu AU - Onji M LA - eng PT - Journal Article PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 187348-17-0 (Interleukin-12) RN - 63231-63-0 (RNA) RN - 9007-49-2 (DNA) SB - IM MH - Adult MH - Antigen-Presenting Cells/*immunology MH - Chronic Disease MH - DNA/blood MH - Dendritic Cells/*immunology MH - Female MH - Hepatitis B/*immunology MH - Hepatitis B virus/*genetics MH - Humans MH - In Situ Hybridization MH - Interleukin-12/blood MH - Male MH - RNA/blood EDAT- 2003/01/15 04:00 MHDA- 2003/08/13 05:00 CRDT- 2003/01/15 04:00 PHST- 2003/01/15 04:00 [pubmed] PHST- 2003/08/13 05:00 [medline] PHST- 2003/01/15 04:00 [entrez] PST - ppublish SO - Int J Mol Med. 2003 Feb;11(2):169-74.