tetano
Editor, Senior Moderator
J Immunol. 2019 Jun 21. pii: ji1801431. doi: 10.4049/jimmunol.1801431. [Epub ahead of print]
[h=1]Early T-BET Expression Ensures an Appropriate CD8[SUP]+[/SUP] Lineage-Specific Transcriptional Landscape after Influenza A Virus Infection.[/h] Prier JE[SUP]1[/SUP], Li J[SUP]1,[/SUP][SUP]2[/SUP], Gearing LJ[SUP]3[/SUP], Olshansky M[SUP]2[/SUP], Sng XYX[SUP]4[/SUP], Hertzog PJ[SUP]3[/SUP], Turner SJ[SUP]5,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Virus infection triggers large-scale changes in the phenotype and function of naive CD8[SUP]+[/SUP] T cells, resulting in the generation of effector and memory T cells that are then critical for immune clearance. The T-BOX family of transcription factors (TFs) are known to play a key role in T cell differentiation, with mice deficient for the TF T-BET (encoded by Tbx21) unable to generate optimal virus-specific effector responses. Although the importance of T-BET in directing optimal virus-specific T cell responses is accepted, the precise timing and molecular mechanism of action remains unclear. Using a mouse model of influenza A virus infection, we demonstrate that although T-BET is not required for early CD8[SUP]+[/SUP] T cell activation and cellular division, it is essential for early acquisition of virus-specific CD8[SUP]+[/SUP] T cell function and sustained differentiation and expansion. Whole transcriptome analysis at this early time point showed that Tbx21 deficiency resulted in global dysregulation in early programming events with inappropriate lineage-specific signatures apparent with alterations in the potential TF binding landscape. Assessment of histone posttranslational modifications within the Ifng locus demonstrated that Tbx21 [SUP]-/-[/SUP] CD8[SUP]+[/SUP] T cells were unable to activate "poised" enhancer elements compared with wild-type CD8[SUP]+[/SUP] T cells, correlating with diminished Ifng transcription. In all, these data support a model whereby T-BET serves to promote appropriate chromatin remodeling at specific gene loci that underpins appropriate CD8[SUP]+[/SUP] T cell lineage-specific commitment and differentiation.
Copyright ? 2019 by The American Association of Immunologists, Inc.
PMID: 31227580 DOI: 10.4049/jimmunol.1801431
[h=1]Early T-BET Expression Ensures an Appropriate CD8[SUP]+[/SUP] Lineage-Specific Transcriptional Landscape after Influenza A Virus Infection.[/h] Prier JE[SUP]1[/SUP], Li J[SUP]1,[/SUP][SUP]2[/SUP], Gearing LJ[SUP]3[/SUP], Olshansky M[SUP]2[/SUP], Sng XYX[SUP]4[/SUP], Hertzog PJ[SUP]3[/SUP], Turner SJ[SUP]5,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Virus infection triggers large-scale changes in the phenotype and function of naive CD8[SUP]+[/SUP] T cells, resulting in the generation of effector and memory T cells that are then critical for immune clearance. The T-BOX family of transcription factors (TFs) are known to play a key role in T cell differentiation, with mice deficient for the TF T-BET (encoded by Tbx21) unable to generate optimal virus-specific effector responses. Although the importance of T-BET in directing optimal virus-specific T cell responses is accepted, the precise timing and molecular mechanism of action remains unclear. Using a mouse model of influenza A virus infection, we demonstrate that although T-BET is not required for early CD8[SUP]+[/SUP] T cell activation and cellular division, it is essential for early acquisition of virus-specific CD8[SUP]+[/SUP] T cell function and sustained differentiation and expansion. Whole transcriptome analysis at this early time point showed that Tbx21 deficiency resulted in global dysregulation in early programming events with inappropriate lineage-specific signatures apparent with alterations in the potential TF binding landscape. Assessment of histone posttranslational modifications within the Ifng locus demonstrated that Tbx21 [SUP]-/-[/SUP] CD8[SUP]+[/SUP] T cells were unable to activate "poised" enhancer elements compared with wild-type CD8[SUP]+[/SUP] T cells, correlating with diminished Ifng transcription. In all, these data support a model whereby T-BET serves to promote appropriate chromatin remodeling at specific gene loci that underpins appropriate CD8[SUP]+[/SUP] T cell lineage-specific commitment and differentiation.
Copyright ? 2019 by The American Association of Immunologists, Inc.
PMID: 31227580 DOI: 10.4049/jimmunol.1801431