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

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.

Etiology of esophageal food impactions in children.

OBJECTIVE: The aim of the study was to measure clinicopathological features of children presenting to a tertiary care emergency department with esophageal food impaction. MATERIALS AND METHODS: A retrospective chart review of children with esophageal food impaction seen between January 1, 2005 and June 30, 2009, including all patients from age 1 month to 18 years with esophageal food impaction at a pediatric emergency department, was performed. RESULTS: Initial screening of International Classification of Disease, 9th Revision, discharge diagnosis identified 698 children with an esophageal foreign body. Of this group, 72 esophageal food impaction events were identified in 65 children (69% boys), 49 of whom required endoscopic intervention. Endoscopic appearances of the esophageal mucosa were abnormal in 40 (82%), revealing evidence of esophagitis (55%) or stricture (27%). Twenty-four of the subjects had biopsies taken at the time of endoscopy. Inflammation, described as increased eosinophils, basilar hyperplasia, rete peg elongation, and/or microabscess, was present in 76% of mucosal samples. Follow-up endoscopy in 12 children identified an etiology in 9, five of whom were found to have eosinophilic esophagitis. CONCLUSIONS: The majority of children with esophageal food impaction who underwent endoscopic evaluation and biopsy have an underlying potentially treatable cause. We therefore recommend that all of the children with esophageal food impaction have mucosal biopsies at the time of endoscopic disimpaction with appropriate follow-up to allow for diagnosis and management of the underlying etiology.

Innate immune function in placenta and cord blood of hepatitis C--seropositive mother-infant dyads.

Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in approximately 80% of cases following exposure, the rate of mother-to-child transmission (2-6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and gammadelta-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells.