title: Analysis of CD127 and KLRG1 expression on hepatitis C virus-specific CD8+ T cells reveals the existence of different memory T-cell subsets in the peripheral blood and liver.
abstract: The differentiation and functional status of virus-specific CD8+ T cells is significantly influenced by specific and ongoing antigen recognition. Importantly, the expression profiles of the interleukin-7 receptor alpha chain (CD127) and the killer cell lectin-like receptor G1 (KLRG1) have been shown to be differentially influenced by repetitive T-cell receptor interactions. Indeed, antigen-specific CD8+ T cells targeting persistent viruses (e.g., human immunodeficiency virus and Epstein-Barr virus) have been shown to have low CD127 and high KLRG1 expressions, while CD8+ T cells targeting resolved viral antigens (e.g., FLU) typically display high CD127 and low KLRG1 expressions. Here, we analyzed the surface phenotype and function of hepatitis C virus (HCV)-specific CD8+ T cells. Surprisingly, despite viral persistence, we found that a large fraction of peripheral HCV-specific CD8+ T cells were CD127+ and KLRG1- and had good proliferative capacities, thus resembling memory cells that usually develop following acute resolving infection. Intrahepatic virus-specific CD8+ T cells displayed significantly reduced levels of CD127 expression but similar levels of KLRG1 expression compared to the peripheral blood. These results extend previous studies that demonstrated central memory (CCR7+) and early-differentiated phenotypes of HCV-specific CD8+ T cells and suggest that insufficient stimulation of virus-specific CD8+ T cells by viral antigen may be responsible for this alteration in HCV-specific CD8+ T-cell differentiation during chronic HCV infection.
authors.affiliation: Department of Medicine II, University of Freiburg, Freiburg, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Bengsch
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Spangenberg
authors.forename: Nadine
authors.initials: N
authors.lastname: Kersting
authors.forename: Christoph
authors.initials: C
authors.lastname: Neumann-Haefelin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Panther
authors.forename: Fritz
authors.initials: F
authors.lastname: von Weizsäcker
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Pircher
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
mesh_terms: D000208:Acute Disease; D000328:Adult; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000821:virology; D006801:Humans; D007156:Immunologic Memory; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D053699:Interleukin-7 Receptor alpha Subunit; C113413:KLRG1 protein, human; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D015534:Trans-Activators