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Published (Version of Record)CC BY V4.0, Open Access
Journal article
Analysis of FOXP3+ Regulatory T Cells That Display Apparent Viral Antigen Specificity during Chronic Hepatitis C Virus Infection
PLoS Pathogens, Vol.5(12), e1000707
2009
Abstract
We reported previously that a proportion of natural CD25+ cells isolated from the PBMC of HCV patients can further upregulate CD25 expression in response to HCV peptide stimulation in vitro, and proposed that virus-specific regulatory T cells (Treg) were primed and expanded during the disease. Here we describe epigenetic analysis of the FOXP3 locus in HCV-responsive natural CD25+ cells and show that these cells are not activated conventional T cells expressing FOXP3, but hard-wired Treg with a stable FOXP3 phenotype and function. Of ∼46,000 genes analyzed in genome wide transcription profiling, about 1% were differentially expressed between HCV-responsive Treg, HCV-non-responsive natural CD25+ cells and conventional T cells. Expression profiles, including cell death, activation, proliferation and transcriptional regulation, suggest a survival advantage of HCV-responsive Treg over the other cell populations. Since no Treg-specific activation marker is known, we tested 97 NS3-derived peptides for their ability to elicit CD25 response (assuming it is a surrogate marker), accompanied by high resolution HLA typing of the patients. Some reactive peptides overlapped with previously described effector T cell epitopes. Our data offers new insights into HCV immune evasion and tolerance, and highlights the non-self specific nature of Treg during infection.
Details
- Title
- Analysis of FOXP3+ Regulatory T Cells That Display Apparent Viral Antigen Specificity during Chronic Hepatitis C Virus Infection
- Authors/Creators
- S. Liu (Author/Creator)S. Floess (Author/Creator) - Charité - Universitätsmedizin BerlinA. Hamann (Author/Creator) - Charité - Universitätsmedizin BerlinS. Gaudieri (Author/Creator) - School of Anatomy, Physiology and Human BiologyA. Lucas (Author/Creator) - Centre for Clinical Immunology and Biomedical Statistics, Perth, Western Australia, AustraliaM. Hellard (Author/Creator) - Burnet InstituteS. Roberts (Author/Creator) - The Alfred HospitalG. Paukovic (Author/Creator) - Burnet InstituteM. Plebanski (Author/Creator) - Monash UniversityB.E. Loveland (Author/Creator) - Burnet InstituteC. Aitken (Author/Creator) - Burnet InstituteS. Barry (Author/Creator) - Women's & Children's Health Research InstituteL. Schofield (Author/Creator) - Walter and Eliza Hall Institute of Medical ResearchE.J. Gowans (Author/Creator) - Monash University
- Publication Details
- PLoS Pathogens, Vol.5(12), e1000707
- Identifiers
- 991005540704507891
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.487 Regulatory T Cells
- Web Of Science research areas
- Microbiology
- Parasitology
- Virology
- ESI research areas
- Microbiology