Catalog Home Page

Analysis of FOXP3+ Regulatory T Cells That Display Apparent Viral Antigen Specificity during Chronic Hepatitis C Virus Infection

Liu, S., Floess, S., Hamann, A., Gaudieri, S., Lucas, A., Hellard, M., Roberts, S., Paukovic, G., Plebanski, M., Loveland, B.E., Aitken, C., Barry, S., Schofield, L. and Gowans, E.J. (2009) Analysis of FOXP3+ Regulatory T Cells That Display Apparent Viral Antigen Specificity during Chronic Hepatitis C Virus Infection. PLoS Pathogens, 5 (12). e1000707.

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (942kB) | Preview
Free to read: https://doi.org/10.1371/journal.ppat.1000707
*No subscription required

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.

Publication Type: Journal Article
Murdoch Affiliation: School of Veterinary and Life Sciences
URI: http://researchrepository.murdoch.edu.au/id/eprint/37085
Item Control Page Item Control Page

Downloads

Downloads per month over past year