TY - JOUR
T1 - Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans
AU - Vieira Braga, Felipe A
AU - Hertoghs, Kirsten M L
AU - Kragten, Natasja A M
AU - Doody, Gina M
AU - Barnes, Nicholas A
AU - Remmerswaal, Ester B M
AU - Hsiao, Cheng-Chih
AU - Moerland, Perry D
AU - Wouters, Diana
AU - Derks, Ingrid A M
AU - van Stijn, Amber
AU - Demkes, Marc
AU - Hamann, Jörg
AU - Eldering, Eric
AU - Nolte, Martijn A
AU - Tooze, Reuben M
AU - ten Berge, Ineke J M
AU - van Gisbergen, Klaas P J M
AU - van Lier, René A W
N1 - © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/10
Y1 - 2015/10
N2 - 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.
AB - 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.
KW - Animals
KW - CD8-Positive T-Lymphocytes/immunology
KW - Cell Line
KW - Cytomegalovirus/immunology
KW - Humans
KW - Influenza A virus/immunology
KW - Interferon-gamma/genetics
KW - Mice
KW - Natural Killer T-Cells/immunology
KW - Positive Regulatory Domain I-Binding Factor 1
KW - Repressor Proteins/genetics
KW - Transcription Factors/genetics
U2 - 10.1002/eji.201545650
DO - 10.1002/eji.201545650
M3 - Article
C2 - 26179882
SN - 0014-2980
VL - 45
SP - 2945
EP - 2958
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 10
ER -