The transcription factor IRF4 impedes human CD8 T-cell function and promotes cells proliferation and PD-1 expression

The transcription factor IRF4 is well known to be quickly upregulated after TCR activation, and magnitude of IRF4 expression is proportional to the strength of TCR activation. However, contradictory reports have been published as to the role of IRF4 in mouse T-cells during acute and chronic viral infections. Furthermore, no data have been published as to the role of IRF4 in human CD8 T-cells, both in normal and pathological conditions. In this work, we subjected CD8 T-cells from healthy donors to IRF4 overexpression or knock-out and assessed the impact of these modifications on T-cell functions and transcriptome. Overall design: CD8 T-cells isolated from PBMC of hemochromatosis donors were subjected to lentiviral transduction or CRISPR Cas9 to induce or delete IRF4 expression, respectively. Cells were then activated or not in vitro for 5h with coated anti-CD3. IRF4 overxpressing or IRF4 KO CD8 T-cells were FACS sorted before RNA sequencing. IRF4 overexpressing cells were compared to RFP (ctrl gene) overexpressing cells, while IRF4 KO cells were compared to CD8 T-cells nucleofected with a ctrl gRNA.