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

Abstract

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.

CD4+ and CD8+ T Cell Activation in Children with Hepatitis C

“…Some studies suggest a role for innate immune cells including neutrophils, 25 natural killer, 26,27 and dendritic cells 27 in the pathogenesis of HCV in children. Other studies point to a role for T cells suggesting increased activation and a shift to an inflammatory (Th1) pattern of cytokine production in children with vertically transmitted HCV infection 28 and protection mediated by CD4 + T cell responses.…”

Alterations in immunophenotype of peripheral blood mononuclear cells in children with chronic viral hepatitis following anti-viral therapy

“…It comprised HCV infected (n = 13) and HBV infected (n = 10) children previously tested prior treatment. Their peripheral blood lymphocytes were thoroughly examined by flow cytometry [6]. The selected group consisted of boys (n = 14) and girls (n = 9) in age from 10 to 20 years, mean 14.4 years ( Table 1).…”

“…These include cellular immune effectors such as T lymphocytes, which become accumulated in liver parenchyma and impose damage to hepatocytes [2]. Only a small portion of these cellular immune effectors sensitized to viral antigens (1-2%), nevertheless the majorities of infiltrating cells becomes activated and are able to induce cell apoptosis in non-specific way [3][4][5][6][7][8][9][10]. The influx of lymphocytes into the liver may result in cellular alterations in the bloodstream.…”

“…Besides, percentage of T cells was increased, predominantly with features of activation. Moreover, antigen presenting cells (APC), in terms of phenotype corresponding to dendritic cells (DCs) of myeloid origin were also upregulated in HCV infected children as compared to uninfected ones [6]. It seemed of interest to search, what happened in the same children within their white blood cell immunophenotype after the full course of anti-viral therapy, based on interferon-α (IFN-α) the drug of choice in these diseases and, at the same time well known immunoregulatory cytokine [8].…”

Hepatitis C Virus' initial encounters: mechanisms of innate immunity

“…Recently a clear understanding of the mechanisms of DC have developed due to their their direct interaction with cells of cytotoxic potential such as CD8 + CD28 -T cells, NK and NKT cells and their role in the pathogenesis of disease (45,69). Their interaction with these cells leads to NK cell activation as evidenced by the upregulation of MICA/B in response to IFN alpha which is impaired in chronic HCV (70).The quantities of these cells in the liver also tend to increase while needed T H cells as well as the ratio of CD4:CD8 T cells decreases (71). DCs can also be implicated in the downregulation of type I IFNs by HCV or be directly affected by diminished IFN production mediated by decreased IL-15 production (70,72).…”