PMID- 18835391
OWN - NLM
STAT- MEDLINE
DCOM- 20090106
LR  - 20240430
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Linking)
VI  - 135
IP  - 6
DP  - 2008 Dec
TI  - Myeloid dendritic cells of patients with chronic HCV infection induce 
      proliferation of regulatory T lymphocytes.
PG  - 2119-27
LID - 10.1053/j.gastro.2008.07.082 [doi]
AB  - BACKGROUND & AIMS: Dendritic cells (DCs) initiate and sustain an efficient 
      T-lymphocyte response. Chronic hepatitis C virus (HCV) infection is associated 
      with inefficient T-cell functions that fail to eradicate the virus, so defects in 
      DC function might be involved in HCV pathogenesis. This study analyzed the 
      activities of myeloid DCs and distinct CD4(+) T-cell populations in samples 
      collected from patients with HCV. METHODS: The abilities of primary BDCA1(+) or 
      monocyte-derived DCs from HCV patients (HCV-DC) to stimulate CD4(+), 
      CD4(+)CD25(-), or different ratios of CD4(+)CD25(+)/CD4(+)CD25(-) T cells were 
      evaluated in mixed lymphocyte reactions. T-cell proliferation and phenotype were 
      evaluated by flow cytometry; cytokine production was evaluated by enzyme-linked 
      immunosorbent assay and marker expression by polymerase chain reaction analyses. 
      RESULTS: HCV-DCs were poor activators of CD4(+) T cells; this defect was reversed 
      by addition of interleukin-2, neutralization of interleukin-10, or elimination of 
      CD4(+)CD25(+) T cells. HCV-DC stimulated proliferation of regulatory T cells 
      (Tregs; CD4(+)CD25(+)FoxP3(+)), which limit proliferation of HCV-specific T 
      lymphocytes. We observed an increased frequency of CD4(+)CD25(+) T cells in 
      peripheral blood of HCV patients and that HCV-DC overexpressed a number of 
      alternative costimulatory molecules, including PD-L1. Finally, HCV-DC stimulated 
      expansion rather than de novo induction of FoxP3(+) Tregs. CONCLUSIONS: Our 
      results indicate a role for myeloid DC in expansion of Tregs to promote chronic 
      infection of patients with HCV.
FAU - Dolganiuc, Angela
AU  - Dolganiuc A
AD  - University of Massachusetts Medical School, Department of Medicine, Worcester, 
      Massachusetts 01605-2324, USA.
FAU - Paek, Edward
AU  - Paek E
FAU - Kodys, Karen
AU  - Kodys K
FAU - Thomas, Joanne
AU  - Thomas J
FAU - Szabo, Gyongyi
AU  - Szabo G
LA  - eng
GR  - R01 AA014372/AA/NIAAA NIH HHS/United States
GR  - DK32520/DK/NIDDK NIH HHS/United States
GR  - 5P30 AI42845/AI/NIAID NIH HHS/United States
GR  - AA014372/AA/NIAAA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080807
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Cytokines)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Cell Proliferation
MH  - Cytokines/biosynthesis/genetics
MH  - Dendritic Cells/*immunology/pathology
MH  - Disease Progression
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Gene Expression
MH  - Hepatitis C, Chronic/*immunology/metabolism/pathology
MH  - Humans
MH  - Myeloid Cells/*immunology/pathology
MH  - RNA/genetics
MH  - T-Lymphocytes, Regulatory/immunology/*pathology
EDAT- 2008/10/07 09:00
MHDA- 2009/01/07 09:00
CRDT- 2008/10/07 09:00
PHST- 2007/09/25 00:00 [received]
PHST- 2008/07/22 00:00 [revised]
PHST- 2008/07/31 00:00 [accepted]
PHST- 2008/10/07 09:00 [entrez]
PHST- 2008/10/07 09:00 [pubmed]
PHST- 2009/01/07 09:00 [medline]
AID - S0016-5085(08)01454-6 [pii]
AID - 10.1053/j.gastro.2008.07.082 [doi]
PST - ppublish
SO  - Gastroenterology. 2008 Dec;135(6):2119-27. doi: 10.1053/j.gastro.2008.07.082. 
      Epub 2008 Aug 7.