Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 45, Issue 10, Pages 2945-2958Publisher
WILEY
DOI: 10.1002/eji.201545650
Keywords
CD8 T cells; NK cells; Transcription factors
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Funding
- Vidi grant from Netherlands Organization of Scientific Research [917.13.338]
- Vici grant from The Netherlands Organization of Scientific Research [918.46.606]
- Dutch Kidney Foundation [C03.2034]
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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- 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- expression within the CD8(+) T-cell population. Furthermore, Hobit was both necessary and sufficient for the production of IFN-. These data implicate Hobit as a novel transcriptional regulator in quiescent human effector-type CD8(+) T cells that regulates their immediate effector functions.
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