TY - JOUR
T1 - Analysis of FOXP3(+) Regulatory T Cells That Display Apparent Viral Antigen Specificity during Chronic Hepatitis C Virus Infection
AU - Li, S.
AU - Floess, S.
AU - Hamann, A.
AU - Gaudieri, Silvana
AU - Lucas, A.
AU - Hellard, M.
AU - Roberts, S.
AU - Paukovic, G.
AU - Plebanski, M.
AU - Loveland, B.E.
AU - Aitken, C.
AU - Barry, S.
AU - Schofield, L.
AU - Gowans, E.J.
PY - 2009
Y1 - 2009
N2 - We reported previously that a proportion of natural CD25+ cells isolated from the PBMC of HCV patients can furtherupregulate CD25 expression in response to HCV peptide stimulation in vitro, and proposed that virus-specific regulatory Tcells (Treg) were primed and expanded during the disease. Here we describe epigenetic analysis of the FOXP3 locus in HCVresponsivenatural CD25+ cells and show that these cells are not activated conventional T cells expressing FOXP3, but hardwiredTreg with a stable FOXP3 phenotype and function. Of ,46,000 genes analyzed in genome wide transcriptionprofiling, about 1% were differentially expressed between HCV-responsive Treg, HCV-non-responsive natural CD25+ cellsand 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 activationmarker is known, we tested 97 NS3-derived peptides for their ability to elicit CD25 response (assuming it is a surrogatemarker), accompanied by high resolution HLA typing of the patients. Some reactive peptides overlapped with previouslydescribed effector T cell epitopes. Our data offers new insights into HCV immune evasion and tolerance, and highlights thenon-self specific nature of Treg during infection.
AB - We reported previously that a proportion of natural CD25+ cells isolated from the PBMC of HCV patients can furtherupregulate CD25 expression in response to HCV peptide stimulation in vitro, and proposed that virus-specific regulatory Tcells (Treg) were primed and expanded during the disease. Here we describe epigenetic analysis of the FOXP3 locus in HCVresponsivenatural CD25+ cells and show that these cells are not activated conventional T cells expressing FOXP3, but hardwiredTreg with a stable FOXP3 phenotype and function. Of ,46,000 genes analyzed in genome wide transcriptionprofiling, about 1% were differentially expressed between HCV-responsive Treg, HCV-non-responsive natural CD25+ cellsand 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 activationmarker is known, we tested 97 NS3-derived peptides for their ability to elicit CD25 response (assuming it is a surrogatemarker), accompanied by high resolution HLA typing of the patients. Some reactive peptides overlapped with previouslydescribed effector T cell epitopes. Our data offers new insights into HCV immune evasion and tolerance, and highlights thenon-self specific nature of Treg during infection.
U2 - 10.1371/journal.ppat.1000707
DO - 10.1371/journal.ppat.1000707
M3 - Article
C2 - 20041222
SN - 1553-7366
VL - 5
SP - -
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 12
ER -