Project description:Anti-CD4 monoclonal antibody, a prominent immunomodulatory agent, elicits robust anti-tumor immunity in various cancers by increasing tumor-infiltrating lymphocytes and promoting CD8+ T cell reactivity against tumor cell-derived antigens. We conducted single-cell transcriptome analysis of anti-CD4-exposed lymphoid cells to investigate the detailed mechanism.
Project description:Dataset release from the Immunological Proteome Resource (ImmPRes). This dataset contains proteomic data from human CD4 and CD8 T cells isolated from PBMC. T-cells were activated with OKT3 antibody (anti CD3) and IL-2 for three days, then expanded in IL-2 until day 7. Cells were then sorted into live CD4 and CD8 T-cells.
Project description:Anti-CD4 monoclonal antibody, a prominent immunomodulatory agent, elicits robust anti-tumor immunity in various cancers by increasing tumor-infiltrating lymphocytes and promoting CD8+ T cell reactivity against tumor cell-derived antigens. We conducted TCR repertoire analysis of anti-CD4-exposed endogenous CD8+ T cells to investigate the expansion pattern of the cell population.
Project description:Autoimmune diseases are characterized by regulatory deficit in both the CD4+ and CD8+ T-cell compartments. We have shown that CD8+ T-cells associated with acute relapse of multiple sclerosis are significantly deficient in their immune suppressive ability. We hypothesized that distinct CD8+ cytotoxic T-cell (Tc) lineages, determined by cytokine milieu during naïve T-cell differentiation, may harbor differential ability to suppress effector CD4+ T-cells. We differentiated purified human naïve CD8+ T-cells in vitro toward Tc0 (media control), Tc1 and Tc17 lineages. Using in vitro flow cytometric suppression assays, we observed that Tc0 and Tc17 cells had similar suppressive ability. In contrast, Tc1 cells showed significant loss of suppressive ability against ex vivo CD4+ T-cells and in vitro-differentiated Th0, Th1 and Th17 cells. Of note, Tc1 cells were also suboptimal in suppressing CD4-induced acute xenogeneic graft versus host disease (xGVHD) in vivo. Tc subtypes derived under various cytokine combinations revealed that IL-12-containing conditions resulted in less suppressive cells exhibiting dysregulated cytotoxic degranulation. RNASeq transcriptome analyses indicated differential regulation of inflammatory genes and enrichment in GM-CSF-associated pathways. These studies provide insights into the role of T-cell differentiation in CD8 suppressive biology and may reveal therapeutically targetable pathways to reverse suppressive deficit during immune-mediated disease.
Project description:In the VILLIN-HA/CL4-TCR transgenic mouse model a population of CD8 T cells with suppressive capacities was indentified. For the molecular characterisation of CD8 regulatory T cells gene comparative expression profiles of naive, activated and regulatory CD8 T cells were performed. Three population of CD8 T cells are included in the analysis. 1. CD8 T cells 2. in vivo activated CD8 T cells 3. in vivo generated CD8 regulatory T cells
Project description:Anti-CD4 monoclonal antibody, a prominent immunomodulatory agent, enriches IL18Rαhi CD8+ T cells that elicit robust anti-tumor immunity in B16F10 melanoma. To investigate gene-expression profile of IL18Rαhi subset, we conducted transcriptome analysis.
Project description:Depletion of CD4+ cells by anti-CD4 monoclonal antibody (anti-CD4 mAb) induces expansion of tumor-reactive CD8+ T cells and exhibits strong antitumor effects in several murine tumor models. However, whether the anti-CD4 mAb treatment activates particular or a broad variety of tumor-reactive CD8+ T cell clones is not answered. To investigate the changes of TCR repertoire induced by the anti-CD4 mAb treatment, we performed unbiased high throughput TCR sequencing in a B16F10 mouse subcutaneous melanoma model.
Project description:Using a CRISPR/Cas9-based approach, we engineered human primary CD4+ and CD8+ T cells in which a bait protein (LAT, SLP76, VAV1 or ZAP70) was tagged with an affinity Twin-Strep-tag (OST), with the purpose of determining by quantitative mass spectrometry the composition and dynamics of the signalosome assembling around each of these signaling proteins prior to and following T cell activation. Affinity purification of the OST tagged protein was performed using Streptactin beads, from T cells left non-stimulated, or stimulated for 30s, 60s, 120s, or 300s with anti-CD3 and anti-CD28 antibodies. Each AP-MS purification is associated with a corresponding control (purification from non-edited WT CD4+ or CD8+ T cells, cultured and stimulated in the same conditions). The number of replicate biological experiments was n=3 for all time-points, and each sample was analyzed twice by single-run nano LC-MS.