Analysis of FOXP3+ regulatory T cells that display apparent viral antigen specificity during chronic hepatitis C virus infection

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dc.contributor.authorLi, S.
dc.contributor.authorFloess, S.
dc.contributor.authorHamann, A.
dc.contributor.authorGaudieri, S.
dc.contributor.authorLucas, A.
dc.contributor.authorHellard, M.
dc.contributor.authorRoberts, S.
dc.contributor.authorPaukovic, G.
dc.contributor.authorPlebanski, M.
dc.contributor.authorLoveland, B.
dc.contributor.authorAitken, C.
dc.contributor.authorBarry, S.
dc.contributor.authorSchofield, L.
dc.contributor.authorGowans, E.
dc.contributor.editorJohn, W.E.
dc.date.issued2009
dc.description.abstractWe 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.
dc.description.statementofresponsibilityShuo 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
dc.identifier.citationPLoS Pathogens, 2009; 5(12):1000707-1-1000707-13
dc.identifier.doi10.1371/journal.ppat.1000707
dc.identifier.issn1553-7366
dc.identifier.issn1553-7374
dc.identifier.orcidBarry, S. [0000-0002-0597-7609]
dc.identifier.orcidGowans, E. [0000-0002-4274-8311]
dc.identifier.urihttp://hdl.handle.net/2440/57012
dc.language.isoen
dc.publisherPublic Library of Science
dc.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.
dc.source.urihttps://doi.org/10.1371/journal.ppat.1000707
dc.subjectT-Lymphocyte Subsets
dc.subjectHumans
dc.subjectHepatitis C, Chronic
dc.subjectAntigens, Viral
dc.subjectEpitopes, T-Lymphocyte
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectFlow Cytometry
dc.subjectCell Separation
dc.subjectGene Expression Profiling
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectImmune Tolerance
dc.subjectEpigenesis, Genetic
dc.subjectT-Lymphocytes, Regulatory
dc.subjectForkhead Transcription Factors
dc.subjectInterleukin-2 Receptor alpha Subunit
dc.subjectImmune Evasion
dc.titleAnalysis of FOXP3+ regulatory T cells that display apparent viral antigen specificity during chronic hepatitis C virus infection
dc.typeJournal article
pubs.publication-statusPublished

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