Project description:T-helper (Th) cells actively communicate with adjacent cells by secreting soluble mediators, and yet crosstalk between Th cells and endothelial cells is poorly understood. Placental growth factor (PlGF), originally identified in the placenta, is an angiogenic factor homologous to vascular endothelial growth factor (VEGF)-A. We performed transcriptome analysis to systemically compare the effect of IL6, a key factor in Th cell polarization, and PlGF on T cell functions.
Project description:To broadly assess which pathways FRCs regulate in CD8+ T cells, we sorted CD8+ T cells for RNA-seq following activation in whole splenocyte mixtures via soluble anti-CD3/CD28 for 48 hours (Stim), activated with anti-CD3/CD28 in the presence of Nos2–/– FRCs (FRC) or activated with anti-CD3/CD28 plus 100 ng/ml recombinant IL-6 (IL-6). Here we demonstrate that FRC-derived signals, including IL-6, act in concert with TCR signaling and co-stimulation to promote the expression of MYC and HIF-1-dependent glycolytic genes and vital pro-survival genes (encoding BCL-2 family members, inhibitors of apoptosis [IAPs] members and Cflar) in activated CD8+ T cells.
Project description:To broadly assess which pathways FRCs regulate in CD8+ T cells, we sorted CD8+ T cells for ATAC-seq following activation in whole splenocyte mixtures via soluble anti-CD3/CD28 (0.25μg/ml) for 48 hours (Stim), activated with anti-CD3/CD28 in the presence of Nos2–/– FRCs (FRC) or activated with anti-CD3/CD28 plus 100 ng/ml recombinant IL-6 (IL-6). Here we demonstrate that FRC-derived signals, including IL-6, act in concert with TCR signaling and co-stimulation to remodel chromatin and render essential transcription factor binding motifs accessible in activated CD8+ T cells. Signals from FRCs led to increased binding regions for MYC, HIF-1α and HIF-1β, which are known to promote metabolic pathways following T cell activation. Additionally, FRC-derived signals promoted activity of transcription factors that regulate survival and memory programs in T lymphocytes such as BATF and BACH2.
Project description:Transcriptional profiling of Double Negative (CD4-/CD8-) T-cells isolated from SIV infected Sooty Mangebys. DN T-cells were stimulated through the T-Cell receptor using anti CD3/CD28 antibodies for 4 hours and compared to unstimulated DN T-cells.
Project description:Fe-IMAC phosphoproteomics using TMT 11plex for quant, of Jurkat T cells stimulated with CD3 and CD28 agonist antibodies for 0, 3, 9, or 27 minutes.
Project description:Background: Binding of the programmed death-1 (PD-1) receptor to its ligands (PD-L1/2) transduces inhibitory signals that promote exhaustion of activated T cells. Blockade of the PD 1 pathway is widely used for cancer treatment, yet the inhibitory signals transduced by PD-1 in T cells remain elusive. Methods: Expression profiles of human CD8+ T cells in resting, activated (CD3+CD28) and PD-1-stimulated cells (CD3+CD28+PD-L1-Fc) conditions were evaluated by RNA-seq. Bioinformatic analyses were used to identify signaling pathways differentially regulated in PD 1-stimulated cells.