title: Correlates and characteristics of hepatitis C virus-specific T-cell immunity in exposed uninfected high-risk prison inmates.
abstract: Some hepatitis C (HCV)-uninfected, high-risk individuals have HCV-specific cellular immunity without viraemia or seroconversion. The characteristics of these responses and the risk behavioural associations were studied in 94 subjects in a prospective cohort of recently seronegative prisoners reporting injecting drug use (IDU). Detailed behavioural data were collected. HCV antibody and PCR testing were performed. ELISpot assays for HCV-induced interferon (IFN)-γ and interleukin (IL)-2 production by T lymphocytes, as well as multiplex in vitro cytokine production assays, were performed. Seventy-eight subjects remained antibody and PCR negative and 16 seroconverted. Of the seronegative group, 22 (28%) had IFN-γ ELISpot responses in comparison with 13 of the 16 seroconverters (82%). This seronegative immune status was associated positively with injecting anabolic steroids and negatively with a recent break from IDU. The IFN-γ ELISpot responses involved both CD4 and CD8 T lymphocytes and were comparable in magnitude, but narrower in specificity, in uninfected subjects than in seroconverters. A subset of seronegative subjects had HCV-induced cytokine production patterns comparable with the seroconverters with increased production of IFN-γ, IL-2 and tumour necrosis factor (TNF)-α and reduced IL-10 in response to nonstructural peptides. In conclusion, comparable patterns of HCV-specific cellular immunity are found in recently infected subjects and in a minority of high-risk, uninfected subjects. Further characterization of these responses and their protective efficacy will inform HCV vaccine development.
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, Sydney, NSW, Australia. barbcameron55@gmail.com
authors.forename: B
authors.initials: B
authors.lastname: Cameron
authors.forename: S
authors.initials: S
authors.lastname: Galbraith
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Lloyd
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004781:Environmental Exposure; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006801:Humans; D008297:Male; D011329:Prisoners; D055815:Young Adult
chemical_list: D016207:Cytokines