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- Title
Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans.
- Authors
Vieira Braga, Felipe A.; Hertoghs, Kirsten M. L.; Kragten, Natasja A. M.; Doody, Gina M.; Barnes, Nicholas A.; Remmerswaal, Ester B. M.; Hsiao, Cheng‐Chih; Moerland, Perry D.; Wouters, Diana; Derks, Ingrid A. M.; Stijn, Amber; Demkes, Marc; Hamann, Jörg; Eldering, Eric; Nolte, Martijn A.; Tooze, Reuben M.; ten Berge, Ineke J. M.; Gisbergen, Klaas P. J. M.; Lier, René A. W.
- 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.
- Publication
European Journal of Immunology, 2015, Vol 45, Issue 10, p2945
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201545650