Braga, FAV, Hertoghs, KML, Kragten, NAM et al. (16 more authors) (2015) The Blimp-1 homologue Hobit identifies effector-type lymphocytes in humans. European Journal of Immunology, 45 (10). 2945 - 2958. ISSN 0014-2980
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 Homologue 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | CD8 T cells; NK cells; transcription factors |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Haematology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Aug 2015 11:08 |
Last Modified: | 09 Nov 2015 18:49 |
Published Version: | http://dx.doi.org/10.1002/eji.201545650 |
Status: | Published |
Publisher: | Wiley-VCH Verlag |
Identification Number: | 10.1002/eji.201545650 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:88798 |