TCF-1 regulation of CD8+ T cell chromatin accessibility

CD8+ T cell differentiation traditionally results in the emergence of two subsets, Tc1 cells that produce interferon (IFN)-gamma and memory cells that mediate immune protection against pathogen infections. More recently, it has emerged that other specialized CD8+ T cell populations develop in immune responses and are critical to orchestrate complete immune protection. These subsets include tissue-resident memory (Trm) T cells, follicular cytotoxic T cells and two CD8+ T cell subsets that produce interleukin (IL)-17, namely, mucosal-associated invariant T (MAIT) cells and Tc17 cells. Here we investigated the role of TCF-1 in CD8+ T cell differentiation by using Assay for Transposase-Accessible Chromatin sequencing (ATAC-Seq) to determine the chromatin accessibility landscape of CD8+ T cells and how this is controlled by TCF-1. Loss of TCF-1 was associated with global changes in the chromatin architecture in CD8+ T cells leading to increased accessibility of Rorc and Tc17 effector genes IL-17a and IL-17f in Tc17 cells. In contrast, we observed reduced accessibility of Tbx21, Eomes and Irf4 loci in Tc17 cells, genes normally required for the induction of Tc1 and memory CD8+ T cells ATAC-Seq data were generated from mouse spleen and lymph node CD8+T cells to investigate how TCF-1 controls the chromatin accessibility landscape.