title: Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans.
abstract: Human cytomegalovirus (CMV) induces the formation of effector CD8(+) T cells that are maintained for decades during the latent stage of infection. Effector CD8(+) T cells appear quiescent, but maintain constitutive cytolytic capacity and can immediately produce inflammatory cytokines such as IFN-γ after stimulation. It is unclear how effector CD8(+) T cells can be constitutively maintained in a terminal stage of effector differentiation in the absence of overt viral replication. We have recently described the zinc finger protein Homolog of Blimp-1 in T cells (Hobit) in murine NKT cells. Here, we show that human Hobit was uniformly expressed in effector-type CD8(+) T cells, but not in naive or in most memory CD8(+) T cells. Human CMV-specific but not influenza-specific CD8(+) T cells expressed high levels of Hobit. Consistent with the high homology between the DNA-binding Zinc Finger domains of Hobit and Blimp-1, Hobit displayed transcriptional activity at Blimp-1 target sites. Expression of Hobit strongly correlated with T-bet and IFN-γ expression within the CD8(+) T-cell population. Furthermore, Hobit was both necessary and sufficient for the production of IFN-γ. These data implicate Hobit as a novel transcriptional regulator in quiescent human effector-type CD8(+) T cells that regulates their immediate effector functions.
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Vieira Braga
authors.affiliation: Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Kirsten M L
authors.initials: KM
authors.lastname: Hertoghs
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.|Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Natasja A M
authors.initials: NA
authors.lastname: Kragten
authors.affiliation: Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Doody
authors.affiliation: Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Barnes
authors.affiliation: Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.|Internal Medicine; Renal Transplant Unit, AMC, Amsterdam, The Netherlands.
authors.forename: Ester B M
authors.initials: EB
authors.lastname: Remmerswaal
authors.affiliation: Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Cheng-Chih
authors.initials: CC
authors.lastname: Hsiao
authors.affiliation: Biostatistics and Bioinformatics, AMC, Amsterdam, The Netherlands.
authors.forename: Perry D
authors.initials: PD
authors.lastname: Moerland
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.affiliation: Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Ingrid A M
authors.initials: IA
authors.lastname: Derks
authors.affiliation: Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.|Internal Medicine; Renal Transplant Unit, AMC, Amsterdam, The Netherlands.
authors.forename: Amber
authors.initials: A
authors.lastname: van Stijn
authors.affiliation: Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Demkes
authors.affiliation: Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
authors.affiliation: Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Eldering
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.|Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Nolte
authors.affiliation: Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: Reuben M
authors.initials: RM
authors.lastname: Tooze
authors.affiliation: Internal Medicine; Renal Transplant Unit, AMC, Amsterdam, The Netherlands.
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: ten Berge
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.|Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Klaas P J M
authors.initials: KP
authors.lastname: van Gisbergen
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.|Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: C573415:IFNG protein, human; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D007371:Interferon-gamma; D000074462:Positive Regulatory Domain I-Binding Factor 1
keywords: CD8 T cells; NK cells; Transcription factors