Decreased numbers and impaired function of circulating dendritic cell subsets in patients with chronic hepatitis B infection (R2)

Duan, Xiaojiang; Zhang, Hui; Wang, Min; Li, Hanwei; Liu, Jingchao; Wang, Fusheng

doi:10.1111/j.1440-1746.2004.03529.x

Cited by 58 publications

(42 citation statements)

References 27 publications

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“…It is possible that negative selection, immunological ignorance, peripheral anergy, and dysregulation of lymphokine production can all contribute to hyporesponsiveness in hosts which are continuously exposed to viral Ags (7). In addition, defective Ag presentation cell function in chronic HBV infection has been proposed (8,9), though it is still a controversial issue (10). Knowing the extent to which each of these factors contributes to the hyporesponsiveness will have a profound influence attempting to break the immunological tolerance and thereby terminate the persistent viral infection.…”

Section: H Epatitis B Virus (Hbv)mentioning

confidence: 99%

Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B

Jin

et al. 2006

The Journal of Immunology

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402

363

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CD4+CD25+ regulatory T cells (Treg) have been shown to maintain immune tolerance against self and foreign Ags, but their role in persistent viral infection has not been well-defined. In this study, we investigated whether and where CD4+CD25+ Treg contribute to the development of chronic hepatitis B (CHB). One hundred twenty-one patients were enrolled, including 16 patients with acute hepatitis B, 76 with CHB, and 29 with chronic severe hepatitis B. We demonstrated that in chronic severe hepatitis B patients, the frequencies of CD4+CD25+ Treg in both PBMC and liver-infiltrating lymphocytes were significantly increased and there was a dramatic increase of FoxP3+-cell and inflammatory cell infiltration in the liver compared with healthy controls. In CHB patients, circulating CD4+CD25+ Treg frequency significantly correlates with serum viral load. In acute hepatitis B patients, circulating CD4+CD25+ Treg frequency was initially low and with time, the profile reversed to exhibit an increased number of circulating Treg in the convalescent phase and restored to normal levels upon resolution. In PBMC taken from infected patients, depletion of CD4+CD25+ Treg led to an increase of IFN-γ production by HBV-Ag-stimulated PBMC. In addition, CD4+CD25+ Treg were capable of suppressing proliferation of autologous PBMC mediated by HBV Ags, which probably reflects the generation of HBV-Ag-specific Treg in circulation and in the liver of HBV-infected patients. Together, our findings suggest that CD4+CD25+ Treg play an active role not only in modulating effectors of immune response to HBV infection, but also in influencing the disease prognosis in patients with hepatitis B.

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Section: H Epatitis B Virus (Hbv)mentioning

confidence: 99%

Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B

Jin

et al. 2006

The Journal of Immunology

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402

363

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“…Besides, alterations of DC in our study were limited to cells of myeloid origin, while plasmacytoid ones (CD123 þ ), known to produce IFN-a, apparently were not affected. The latter were shown to be downregulated both in number and in function in adult patients with chronic hepatitis B [28]. Thus, DC subsets require further study in hepatitis C, especially in juvenile population.…”

Section: Discussionmentioning

confidence: 99%

Significance of Alterations in PBMC Immunophenotype of Children with Chronic Viral Hepatitis C – the Role of Dendritic Cells

et al. 2006

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There are differences in the clinical course of chronic viral hepatitis C between adults and children, but it is generally accepted that the disease has cell-mediated immune background. The aim of this study was to evaluate PBMC subsets in children with chronic hepatitis C before treatment in order to find some predictive factors, useful for patients management. Several PBMC subsets, in particular lymphoid and dendritic cell (DC) ones, were tested by flow cytometry in HCV þ paediatric patients (n ¼ 46) and in control children matched in terms of age and sex (n ¼ 20). Data were subjected to extensive statistics. It was found that cells with cytotoxic potential such as CD8 þ CD28 -T cells, NK and NKT cells as well as lineage -HLA-DR þ DC were increased in per cent values, while CD4 þ T cells and CD4:CD8 ratio were decreased in hepatitis C group. In HCV þ patients, CD4 þ T cells were inversely correlated with alanine aminotransferase (ALT) levels and with viraemia. DC subset of myeloid origin (CD11c þ ) assessed both in per cent values and as mean fluorescence intensity (MFI) of HLA-DR expression was shown to be downregulated in hepatitis patients, in spite of increased numbers. To conclude, PBMC subsets, and in particular DC, are affected by HCV chronic infection in children, reflected by the correlation with clinical parameters, such as ALT and viraemia.

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“…In the majority of studies, the function of neonatal DCs has been shown to be defective compared to adult DC function (3,6). Increasing evidence suggests that neonates of HBV carrier mothers are exposed to virions and/or viral antigens in utero even if they do not acquire the infection (17,18,23,30).…”

Section: Discussionmentioning

confidence: 99%

“…The fact that the observed differences within the group of babies born to HBsAg ϩ mothers were not significant might have been due to the small sample number. The mean frequencies of mDCs and pDCs did not exceed 0.4% of total PBMCs until the age of 6 months, and therefore, they are expected to reach adult levels (0.8 to 1%) later in life (6).…”

Section: Discussionmentioning

confidence: 99%

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Dendritic Cells in Uninfected Infants Born to Hepatitis B Virus-Positive Mothers

Koumbi

Papadopoulos

Anastassiadou

et al. 2010

Clin Vaccine Immunol

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Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses via Toll-like receptors (TLR) and producing in response vast amounts of type I interferons (IFNs). Hepatitis B virus (HBV)causes chronic infection after vertical transmission. This study investigated whether an HBV-infected maternal environment might influence DC numbers and pDC function in uninfected infants. Blood was collected from inactive HBsAg carrier and control mothers and their infants at birth and 1 and 6 months of age. HBV DNA was measured in maternal and neonatal perinatal sera using real-time PCR. The circulating frequencies of myeloid DCs (mDCs) and pDCs were determined in the babies by flow cytometry. Peripheral blood mononuclear cells (PBMCs) and cord blood pDCs were stimulated with resiquimod, and alpha interferon (IFN-␣) production and the pDC phenotype were assessed. The effect of the common-cold virus, rhinovirus (RV), on resiquimod stimulation was also determined. HBV DNA was detected in 62.3% of the mothers and 41% of their infants. DC numbers and pDC functions were similar between subjects and controls and were not correlated with maternal or neonatal viremia. RV infection did not induce pDC maturation until the age of 6 months, and it reduced TLR7-dependent resiquimod-induced IFN-␣ production similarly in both groups. Although the DC system is immature at birth, DCs of uninfected neonates of HBV-positive mothers are competent to initiate and maintain T-cell responses. RV is a weak inducer of IFN-␣ production until the age of 6 months and inhibits IFN-␣ responses triggered by the TLR7 pathway.

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Decreased numbers and impaired function of circulating dendritic cell subsets in patients with chronic hepatitis B infection (R2)

Cited by 58 publications

References 27 publications

Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B

Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B

Significance of Alterations in PBMC Immunophenotype of Children with Chronic Viral Hepatitis C – the Role of Dendritic Cells

Dendritic Cells in Uninfected Infants Born to Hepatitis B Virus-Positive Mothers

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