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Type: Journal article
Title: Analysis of FOXP3+ regulatory T cells that display apparent viral antigen specificity during chronic hepatitis C virus infection
Author: Li, S.
Floess, S.
Hamann, A.
Gaudieri, S.
Lucas, A.
Hellard, M.
Roberts, S.
Paukovic, G.
Plebanski, M.
Loveland, B.
Aitken, C.
Barry, S.
Schofield, L.
Gowans, E.
Citation: PLoS Pathogens, 2009; 5(12):1000707-1-1000707-13
Publisher: Public Library of Science
Issue Date: 2009
ISSN: 1553-7366
Statement of
Shuo Li, Stefan Floess, Alf Hamann, Silvana Gaudieri, Andrew Lucas, Margaret Hellard, Stuart Roberts, Geza Paukovic, Magdalena Plebanski, Bruce E. Loveland, Campbell Aitken, Simon Barry, Louis Schofield and Eric J. Gowans
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.
Keywords: T-Lymphocyte Subsets; Humans; Hepatitis C, Chronic; Antigens, Viral; Epitopes, T-Lymphocyte; Oligonucleotide Array Sequence Analysis; Flow Cytometry; Cell Separation; Gene Expression Profiling; Reverse Transcriptase Polymerase Chain Reaction; Immune Tolerance; Epigenesis, Genetic; T-Lymphocytes, Regulatory; Forkhead Transcription Factors; Interleukin-2 Receptor alpha Subunit; Immune Evasion
Rights: © 2009 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0020094775
DOI: 10.1371/journal.ppat.1000707
Appears in Collections:Paediatrics publications

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