Analysis of FOXP3(+) Regulatory T Cells That Display Apparent Viral Antigen Specificity during Chronic Hepatitis C Virus Infection
- Author(s)
- Li, S; Floess, S; Hamann, A; Gaudieri, S; Lucas, A; Hellard, M; Roberts, S; Paukovic, G; Plebanski, M; Loveland, BE; Aitken, C; Barry, S; Schofield, L; Gowans, EJ;
- Details
- Publication Year 2009-12,Volume 5,Issue #12,Page -
- Journal Title
- PLOS PATHOGENS
- Publication Type
- Journal Article
- 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 similar to 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.
- Publisher
- PUBLIC LIBRARY SCIENCE
- Keywords
- IN-VITRO PROLIFERATION; CHRONIC HCV INFECTION; LYMPHOCYTES; SUPPRESSION; EXPRESSION; PHENOTYPE; CYTOKINE; SHARE
- Publisher's Version
- https://doi.org/10.1371/journal.ppat.1000707
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- Refer to copyright notice on published article.
Creation Date: 2009-12-01 12:00:00