Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans

Research output: Contribution to journalArticle

Authors

  • Felipe A Vieira Braga
  • Kirsten M L Hertoghs
  • Natasja A M Kragten
  • Gina M Doody
  • Ester B M Remmerswaal
  • Cheng-Chih Hsiao
  • Perry D Moerland
  • Diana Wouters
  • Ingrid A M Derks
  • Amber van Stijn
  • Marc Demkes
  • Jörg Hamann
  • Eric Eldering
  • Martijn A Nolte
  • Reuben M Tooze
  • Ineke J M ten Berge
  • Klaas P J M van Gisbergen
  • René A W van Lier

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)2945-2958
Number of pages14
JournalEuropean Journal of Immunology
Volume45
Issue number10
Early online date15 Jul 2015
Publication statusPublished - Oct 2015

Keywords

  • Animals, CD8-Positive T-Lymphocytes/immunology, Cell Line, Cytomegalovirus/immunology, Humans, Influenza A virus/immunology, Interferon-gamma/genetics, Mice, Natural Killer T-Cells/immunology, Positive Regulatory Domain I-Binding Factor 1, Repressor Proteins/genetics, Transcription Factors/genetics