title: Gene expression profiles of T cells from hepatitis E virus infected patients in acute and resolving phase.
abstract: OBJECTIVE
  Approximately 50% of acute viral hepatitis in young adults and in pregnant women is due to hepatitis E virus (HEV) infection in developing countries. T cell-mediated immune injury probably plays a key role in the pathogenesis of acute hepatitis illness. However, there is a paucity of data on the global gene expression programs activated on T cells, which are subsequently responsible for T cell recruitment to the liver and triggering of immune injury.
  
  
  METHODS
  We performed a flow cytometric analysis of T cells in individuals with acute hepatitis E (AVH-E; n=10), resolving phase of HEV (n=9), and ten healthy controls (HC). Further transcriptional profiling analysis was performed using Affymetrix GeneChip DNA microarrays to identify the genes that were differentially expressed in AVH-E and HC.
  
  
  RESULTS
  Patients with AVH-E showed higher frequencies of CD8+ (27 ± 4%; P=0.02) and activated CD38+ CD69+ T cells (25% ± 3%; P=0.04) than in resolving phase patients (20 ± 2% and 9.1 ± 4%, respectively), who in turn exhibited higher CCR9 expression than cells from patients in active phase. The naïve T cell population (CD3+ CD45RA+) was decreased upon HEV infection (29 ± 4% in AVH-E vs. 53.1 ± 3.2% in HC; P=0.05); however, the CD11a high subpopulation within CD4+ CD45RA+ cells was increased in both AVH-E (6.1%) and resolving phase (7.7%) patients. Gene ontology analysis suggested that during AVH-E infection, there is in CD4+ T cells an activation of genes involved in pro-inflammatory responses. Additional RT-PCR analysis confirmed that in cells from AVH-E patients, there is an increased expression of CCR5, CCR9, CXCR3, CXCR4, STAT1, IRF-9, IFN-α, and TNF-α, together with a down-regulation of IL-2, SOCS3, and IL-10, with respect to cells from resolving phase patients.
  
  
  CONCLUSIONS
  Our findings suggest the involvement of a circulating CD45RA+ CD11a high population with CCR5 expression in the pathogenesis processes of AVH-E. The obtained results help to understand the underlying inflammatory process occurring in HEV infection, which can lead to either resolution or immunopathology.
authors.affiliation: Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, 110 070, New Delhi, India. trehanpati@gmail.com
authors.forename: Nirupma
authors.initials: N
authors.lastname: TrehanPati
authors.forename: Sukriti
authors.initials: S
authors.lastname: Sukriti
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
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: Carlos A
authors.initials: CA
authors.lastname: Guzman
authors.forename: Shiv Kumar
authors.initials: SK
authors.lastname: Sarin
mesh_terms: D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D040881:CD11a Antigen / Q000096:biosynthesis* / Q000097:blood; D016022:Case-Control Studies; D003289:Convalescence; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016751:Hepatitis E / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000821:virology; D016752:Hepatitis E virus / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000096:biosynthesis* / Q000097:blood; D008099:Liver; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D040881:CD11a Antigen; D019713:Receptors, CCR5; D017493:Leukocyte Common Antigens