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.