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

• Published in: European journal of immunology Vol. 45; no. 10; pp. 2945 - 2958
• Main 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.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.10.2015
• Subjects: Animals; CD8 T cells; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cytomegalovirus; Cytomegalovirus - immunology; Human cytomegalovirus; Humans; Influenza A virus - immunology; Interferon-gamma - genetics; Interferon-gamma - immunology; Lymphocytes; Mice; Natural Killer T-Cells - immunology; NK cells; Positive Regulatory Domain I-Binding Factor 1; Repressor Proteins - genetics; Repressor Proteins - immunology; T cell receptors; Transcription factors; Transcription Factors - genetics; Transcription Factors - immunology; NK cells; Transcription factors; CD8 T cells
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201545650

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.