title: Gene expression signatures of peripheral CD4+ T cells clearly discriminate between patients with acute and chronic hepatitis B infection.
abstract: CD4+ T and regulatory T cells (Tregs) seem to play a key role in persistence of hepatitis B virus (HBV) infection. However, the molecular events by which Tregs exert their modulatory activity are largely unknown. The transcriptional profiles of CD4+ T cells of healthy controls (HCs) and patients affected by acute hepatitis B (AVH-B) or chronic hepatitis B (CHB) infection were established using a custom expression array consisting of 350 genes relevant for CD4+ T cell and Treg function. These studies were complemented by real-time reverse-transcription polymerase chain reaction. Peripheral blood mononuclear cells (PBMCs) were also analyzed for the presence of Tregs, which were more abundant in the acute stage of the disease (7%) than in HCs and CHB infection (HCs versus AVH-B, P = 0.003; AVH-B versus CHB, P = 0.04). One hundred eighteen genes (34%) intrinsically differentiate HBV-infected patients from HCs. Using gene ontology, we identified T cell receptor signaling and clusterization, mitogen-activated protein kinase kinase signaling, cell adhesion, cytokines and inflammatory responses, cell cycle/cell proliferation, and apoptosis as the most prominent affected modules. A higher expression of CCR1, CCR3, CCR4, CCR5, and CCR8 was seen in AVH-B than in CHB-infected patients and HCs. Annotation of the interconnected functional network of genes provided a unique representation of global immune activation during acute infection. Almost all genes were down-regulated in patients with CHB infection.
  
  
  CONCLUSIONS
  The fingerprints enable clear discrimination between patients suffering from AVH-B or CHB infection. The observed profiles suggest accumulation of effector T cells with a potential role in necro-inflammation during the acute stage. Subsequent down-regulated effector functions support the hypothesis of suppressed CD4+ effector T cells favoring viral persistence in the chronic infection stage.
authors.affiliation: Department of Gastroenterology, GB Pant Hospital, New Delhi, India.
authors.forename: Nirupma
authors.initials: N
authors.lastname: TrehanPati
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.lastname: Sukriti
authors.forename: Syed
authors.initials: S
authors.lastname: Hissar
authors.forename: Peggy
authors.initials: P
authors.lastname: Riese
authors.forename: Tanja
authors.initials: T
authors.lastname: Toepfer
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzman
authors.forename: Shiv Kumar
authors.initials: SK
authors.lastname: Sarin
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D006509:Hepatitis B / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D018925:Chemokines; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D018799:Intercellular Adhesion Molecule-1; D020929:Mitogen-Activated Protein Kinase Kinases