title: In vitro activation and differentiation of naïve CD4+ and CD8+ T cells into HCV core- and NS3-specific armed effector cells: a new role for CD4+ T cells.
abstract: Viral clearance in hepatitis C virus (HCV) infection has been correlated with strong, multi-specific and sustained T cell responses. The number of functionally active effector T cells determines the outcome of infection. Only a small number of antigen-specific naïve T cells are originally present. Upon infection, they undergo activation, clonal expansion and differentiation to become effector cells. In this study, we determined the ability of dendritic cells (DCs) to prime T cells in vitro to become effector cells upon stimulation with various TLR ligands or IFNalpha. T cell priming and activation was determined by proliferation and production of effector molecules, IFN-gamma and Granzyme B (GrB). HCV Core-specific T cells showed significant increase in proliferation, and the number of HCV Core-specific CD4+ and CD8+ T cells producing IFN-gamma and GrB was higher than control or NS3-specific T cells. These in vitro-primed CD4+ and CD8+ T cells exhibit the phenotype of just-activated and/or armed effector lymphocytes confirming the transition of naïve T cells to effector cells. This is the first study demonstrating the activation of GrB+CD4+ T cells against antigen(s) derived from HCV. Our study suggests a novel role of CD4+ T cells in immunity against HCV.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alta. T6G 2S2, Canada.
authors.forename: Deepa K
authors.initials: DK
authors.lastname: Krishnadas
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Lorne J
authors.initials: LJ
authors.lastname: Tyrrell
authors.forename: Babita
authors.initials: B
authors.lastname: Agrawal
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes / Q000235:genetics / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D018936:Hepatitis C Antigens / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D053804:Granzymes; D018936:Hepatitis C Antigens; D007371:Interferon-gamma; D012313:RNA; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases