title: CD4+ and CD8+ T Cell Activation in Children with Hepatitis C.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pediatrics, Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver School of Medicine, Aurora, CO.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Sheiko
authors.affiliation: Division of Gastroenterology and Hepatology, Hepatitis C Center, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Lucy
authors.initials: L
authors.lastname: Golden-Mason
authors.affiliation: Division of Gastroenterology and Hepatology, Hepatitis C Center, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giugliano
authors.affiliation: Department of Pediatrics, Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver School of Medicine, Aurora, CO.
authors.forename: Christine Waasdorp
authors.initials: CW
authors.lastname: Hurtado
authors.affiliation: Department of Pediatrics, Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver School of Medicine, Aurora, CO.
authors.forename: Cara L
authors.initials: CL
authors.lastname: Mack
authors.affiliation: Department of Pediatrics, Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver School of Medicine, Aurora, CO.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Narkewicz
authors.affiliation: Division of Gastroenterology and Hepatology, Hepatitis C Center, Department of Medicine, University of Colorado Denver, Aurora, CO; Eastern Colorado Veteran's Affairs Medical Center, Denver, CO. Electronic address: Hugo.Rosen@UCDENVER.edu.
authors.forename: Hugo R
authors.initials: HR
authors.lastname: Rosen
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: C491199:EOMES protein, human; D007376:Interleukin-2; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C534712:TIGIT protein, human; D007371:Interferon-gamma