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

Autor: 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, Eric J Gowans
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: PLoS Pathogens, Vol 5, Iss 12, p e1000707 (2009)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1000707
Popis: 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 approximately 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.
Databáze: Directory of Open Access Journals
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