Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans
Research output: Contribution to journal › Article › peer-review
Authors
Colleges, School and Institutes
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.
Details
Original language | English |
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Pages (from-to) | 2945-2958 |
Number of pages | 14 |
Journal | European Journal of Immunology |
Volume | 45 |
Issue number | 10 |
Early online date | 15 Jul 2015 |
Publication status | Published - Oct 2015 |
Keywords
- Animals, CD8-Positive T-Lymphocytes/immunology, Cell Line, Cytomegalovirus/immunology, Humans, Influenza A virus/immunology, Interferon-gamma/genetics, Mice, Natural Killer T-Cells/immunology, Positive Regulatory Domain I-Binding Factor 1, Repressor Proteins/genetics, Transcription Factors/genetics