2. Academic Validation
  3. Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans

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

  • Eur J Immunol. 2015 Oct;45(10):2945-58. doi: 10.1002/eji.201545650.
Felipe A Vieira Braga 1,  Kirsten M L Hertoghs 2,  Natasja A M Kragten 1 2,  Gina M Doody 3,  Nicholas A Barnes 3,  Ester B M Remmerswaal 2 4,  Cheng-Chih Hsiao 2,  Perry D Moerland 5,  Diana Wouters 1,  Ingrid A M Derks 2,  Amber van Stijn 2 4,  Marc Demkes 2,  Jörg Hamann 2,  Eric Eldering 2,  Martijn A Nolte 1 2,  Reuben M Tooze 3,  Ineke J M ten Berge 4,  Klaas P J M van Gisbergen 1 2,  René A W van Lier 1 2
Affiliations

Affiliations

  • 1 Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.
  • 2 Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
  • 3 Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • 4 Internal Medicine; Renal Transplant Unit, AMC, Amsterdam, The Netherlands.
  • 5 Biostatistics and Bioinformatics, AMC, Amsterdam, The Netherlands.
PMID: 26179882 DOI: 10.1002/eji.201545650
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.

Keywords

CD8 T cells; NK cells; Transcription factors.

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