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

作者：Li Shuo^*; Floess Stefan; Hamann Alf; Gaudieri Silvana; Lucas Andrew; Hellard Margaret; Roberts Stuart; Paukovic Geza; Plebanski Magdalena; Loveland Bruce E; Aitken Campbell; Barry Simon; Schofield Louis; Gowans Eric J

来源：PLoS Pathogens, 2009, 5(12): e1000707.

DOI：10.1371/journal.ppat.1000707

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.

• 出版日期2009-12
• 单位河北医科大学