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

Eur J Immunol. 2015 Oct;45(10):2945-58. doi: 10.1002/eji.201545650. Epub 2015 Sep 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • IFNG protein, human
  • Prdm1 protein, mouse
  • Repressor Proteins
  • Transcription Factors
  • PRDM1 protein, human
  • Interferon-gamma
  • Positive Regulatory Domain I-Binding Factor 1