Hepatitis C virus-specific reactivity of CD4+-lymphocytes in children born from HCV-infected women

Bella, Silvia Della; Riva, Antonio; Tanzi, Elisabetta; Nicola, Stefania; Amendola, Antonella; Vecchi, L.; Nebbia, Gabriella; Longhi, Renato; Zanetti, Alessandro; Villa, Maria Luisa

doi:10.1016/j.jhep.2005.03.022

Cited by 27 publications

(20 citation statements)

References 23 publications

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“…This is an important new finding that may allow better clarification of the significance of DC reduction in these patients. In a similar manner to previous observations in a different setting composed of CHC women and their children, 23 here we could confirm that CD4 + T‐cell‐proliferative responses to HCV peptides are less frequent and vigorous in CHC than in HSP, possibly because of an incomplete cell activation. As in that study, here we could also demonstrate that the production of IL‐10 by PBMCs stimulated with HCV peptides was inversely correlated with CD4 + T‐cell proliferation in CHC patients but not in HSP patients.…”

Section: Discussionsupporting

confidence: 91%

“…The reactivity of CD4 + T cells was assessed by flow cytometry as previously described 23 . The PBMCs were cultured for 6 days without stimulation, or with phytohaemagglutinin (PHA) (10 μg/ml; Sigma), influenza virus vaccine (FLU) (A/Taiwan, A/Shangai, B/Victoria; 24 pg/ml; a kind gift from Prof. Clerici, University of Milan), or 10 μg/ml synthetic HCV peptides.…”

Section: Methodsmentioning

confidence: 99%

“…The PBMCs were cultured for 6 days without stimulation, or with phytohaemagglutinin (PHA) (10 μg/ml; Sigma), influenza virus vaccine (FLU) (A/Taiwan, A/Shangai, B/Victoria; 24 pg/ml; a kind gift from Prof. Clerici, University of Milan), or 10 μg/ml synthetic HCV peptides. One peptide from the core (C39–63), one from the envelope (E 1 238–262), and two from the non‐structural region (NS 3 1384–1401, and NS 3 1406–1415) were used; these had been previously selected as the most immunogenic among 38 peptides chosen from sequences of HCV 1b strain on the basis of their ability to bind to the most common HLA molecules present in the Italian population 23 . A non‐antigenic HIV peptide (p23) was used as negative control.…”

Section: Methodsmentioning

confidence: 99%

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Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus‐specific CD4⁺ T‐cell proliferation in patients with hepatitis C virus infection

et al. 2007

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+ T-cell proliferation was less frequent and vigorous in CHC than in HSP patients and was directly related to the number of PBDCs and their IL-12 production but inversely related to their IL-10 production. Taken together, these results seem to suggest that cytokines of DC origin contribute to the regulation of HCV-specific immunity in CHC patients and indicate that PBDCs may represent a novel non-invasive tool for immune monitoring of these patients.

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Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus‐specific CD4⁺ T‐cell proliferation in patients with hepatitis C virus infection

et al. 2007

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“…We believe these data represent a true immune reaction to HCV rather than cross-reactivity to other antigens (eg, influenza), which would have been similar in all groups 33 . Interestingly, the presence of HCV-specific CMI responses in the absence of anti-HCV was also observed by Della Bella et al, where 71% of children born to mothers infected with HCV had circulating CD4 + lymphocytes reacting against HCV-specific antigens 30 . In a study of adult blood donors, a similar proportion (83%) with a past resolved infection had a positive ELISPOT response 34 .…”

Section: Discussionsupporting

confidence: 69%

Hepatitis C Virus-Specific Cell-Mediated Immune Responses in Children Born to Mothers Infected with Hepatitis C Virus

El-Kamary

Hashem

Saleh

et al. 2013

The Journal of Pediatrics

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ObjectiveTo investigate the association between hepatitis C virus (HCV)-specific cell-mediated immunity (CMI) responses and viral clearance in children born to mothers infected with HCV.Study designA cross-sectional study of children from a mother-infant cohort in Egypt were enrolled to detect CMI responses to recombinant core and nonstructural HCV antigens (nonstructural segments NS3, NS4a/b, and NS5 of the HCV genome) using an interferon-gamma enzyme-linked immunospot assay. Children born to mothers with chronic HCV were enrolled into 3 groups: transiently viremic (n = 5), aviremic (n = 36), and positive control (n = 6), which consisted of 1 child with chronic HCV from this cohort and another 5 children with chronic HCV from a companion study. Children without HCV born to mothers without HCV (n = 27) served as a negative control group. Wilcoxon rank sum test was used to compare the magnitude of CMI responses between groups.ResultsNone of the 6 control children who were positive for HCV responded to any HCV antigen, and 4 (80%) of 5 children with transient viremia responded to at least one HCV antigen, compared with 5 (14%) of 36 and 3 (11%) of 27 children in the aviremic and negative control groups, respectively. Children with transient viremia elicited stronger responses than did negative controls (P = .005), positive controls (P = .011), or children without HCV viremia (P = .012), particularly to nonstructural antigens.ConclusionsHCV-specific CMI responses were significantly higher in magnitude and frequency among transiently infected children compared with those persistently infected. This suggests CMI responses may be associated with past viral clearance and can identify children at high risk of infection, who can be targeted for health education, screening, and follow-up.

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“…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. 29 In another study, neonates exposed to HCV showed a relative suppression of immune activation, which was counterbalanced by an increased production of IFN- γ . 30 …”

mentioning

confidence: 96%

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

Sheiko

Golden-Mason

Giugliano

et al. 2016

The Journal of Pediatrics

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Objectives To assess if peripheral T cell populations in children with chronic hepatitis C virus (HCV) infection would show evidence of activation/exhaustion and an attenuated functional response. Study design Compared with adults, children with HCV infection have a higher rate of spontaneous viral clearance. In adults, chronic HCV has been linked to T cell exhaustion. Little is known of the immune status of children with HCV. Peripheral blood mononuclear cells were isolated from 16 children with HCV (6 males, 10 females; mean age 8.6 years, range 2-17), 16 age- and sex-matched control children without HCV infection, and 20 adults with chronic HCV. Multiparameter flow cytometry was performed to characterize T cell differences across the 3 groups. Results Controls and children with HCV had similar levels of CD4+, CD8+, and γδ+ T cells. Children with HCV demonstrated a decrease in naïve T cells compared with control children and increased activation/exhaustion marker expression on both CD8+ and CD4+ T cells. Transcription factor analysis suggested functional activation of T cells in children with HCV; however, only the CD4+ subset had enhanced cytokine production (interferon gamma and interleukin-2) compared with control children. Conclusions The HCV response in children is characterized by several changes in T cell phenotype. Many of these changes, such as increased T cell expression of programmed cell death-1, are similar to responses in adults. Of note, cytokine production by CD4+ helper T cells is increased in children with HCV compared with age- and sex-matched control children, which may influence long-term prognosis in children with HCV.

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Hepatitis C virus-specific reactivity of CD4+-lymphocytes in children born from HCV-infected women

Cited by 27 publications

References 23 publications

Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus‐specific CD4⁺ T‐cell proliferation in patients with hepatitis C virus infection

Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus‐specific CD4⁺ T‐cell proliferation in patients with hepatitis C virus infection

Hepatitis C Virus-Specific Cell-Mediated Immune Responses in Children Born to Mothers Infected with Hepatitis C Virus

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

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Hepatitis C virus-specific reactivity of CD4+-lymphocytes in children born from HCV-infected women

Cited by 27 publications

References 23 publications

Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus‐specific CD4+ T‐cell proliferation in patients with hepatitis C virus infection

Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus‐specific CD4+ T‐cell proliferation in patients with hepatitis C virus infection

Hepatitis C Virus-Specific Cell-Mediated Immune Responses in Children Born to Mothers Infected with Hepatitis C Virus

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

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Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus‐specific CD4⁺ T‐cell proliferation in patients with hepatitis C virus infection

Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus‐specific CD4⁺ T‐cell proliferation in patients with hepatitis C virus infection