Journal article
High resolution analysis of cellular immune responses in resolved and persistent hepatitis C virus infection
Gastroenterology, Vol.127(3), pp.924-936
2004
Abstract
Background & Aims: Cellular immune responses are thought to play a key role in the resolution of primary HCV infection. Although it has been consistently shown that CD4+ T-cell responses are maintained in those with spontaneous resolution but lost in those with persistent infection, the role of CD8+ T-cell responses remains controversial. Previous studies have largely focused on limited HLA alleles and predefined CD8+ T-cell epitopes, and, thus, comprehensive studies remain to be performed.
Methods: To understand the composition of the immune response associated with spontaneous resolution, we comprehensively mapped CD8+ T-cell responses in 20 HLA-diverse persons with resolved HCV infection, using HCV peptides spanning the entire genome. We analyzed the magnitude, breadth, function, and phenotype using ELISpot, class-I tetramers, intracellular cytokine staining, and cytolytic assays. We studied in parallel HCV-specific responses and viral sequence variation in persistent infection.
Results: Responses in individuals with resolved infection were strong and broad with robust proliferation in response to antigen. Responses in those persistently infected were rarely detected ex vivo and, when present, were narrowly directed and weak. However, they also proliferated in vitro. Dominant target epitopes differed among individuals in both cohorts, despite frequently shared HLA-alleles.
Conclusions: These data indicate that persisting, strong CD8+ T-cell responses are observed in the majority of persons with resolved HCV infection and provide support for strategies to boost CD8+ T-cell responses for the prevention or treatment of HCV infection but also highlight the diversity of responses that may need to be elicited to provide protection.
Details
- Title
- High resolution analysis of cellular immune responses in resolved and persistent hepatitis C virus infection
- Authors/Creators
- G.M. Lauer (Author/Creator) - Harvard UniversityE. Barnes (Author/Creator) - The Royal Free HospitalM. Lucas (Author/Creator) - University of OxfordJ. Timm (Author/Creator) - Harvard UniversityK. Ouchi (Author/Creator) - Harvard UniversityA.Y. Kim (Author/Creator) - Harvard UniversityC.L. Day (Author/Creator) - Harvard UniversityG.K. Robbins (Author/Creator) - Harvard UniversityD.R. Casson (Author/Creator) - Massachusetts General HospitalM. Reiser (Author/Creator) - Universitätsklinikum Knappschaftskrankenhaus BochumG. Dusheiko (Author/Creator)T.M. Allen (Author/Creator) - Harvard UniversityR.T. Chung (Author/Creator) - Massachusetts General HospitalB.D. Walker (Author/Creator) - Howard Hughes Medical InstituteP. Klenerman (Author/Creator) - University of Oxford
- Publication Details
- Gastroenterology, Vol.127(3), pp.924-936
- Publisher
- Elsevier
- Identifiers
- 991005539592107891
- Copyright
- © Elsevier Ltd
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.125 Hepatitis
- 1.125.83 HCV
- Web Of Science research areas
- Gastroenterology & Hepatology
- ESI research areas
- Clinical Medicine