Project description:CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of different immune cells. They are known to play crucial roles in antibody class switching in B cells, neutrophil recruitment and activation of macrophages and CD8+ cytotoxic T cells. The activation and functional status of CD4+ T cells is important for adequate responses to pathogen infections but has also been associated with auto-immune disorders and survival in several cancers. In the current study, we carried out proteomic profiling of resting and activated primary human CD4+ T cells from healthy donors. In addition to identifying known markers of CD4+ T cell activation, we also identified protein kinases, protein phosphatases, and cytokines to be differentially expressed.
Project description:To investigate the function of Bcl11b in activated C57Bl/6 mouse CD4+ T cells, we deleted Bcl11b in vivo using a Bcl11b-fl/fl;Cd4cre-ert2 tamoxifen-inducible strategy. We then cultured CD4 T cells isolated from these mice 3 days in resting or activating condtions. Finally, we performed gene expression profiling analysis using data obtained from RNA-seq of 3-5 samples per genotype per condition.
Project description:This SuperSeries is composed of the following subset Series: GSE18524: Identification of the Early VIP Transriptome and its Associated Interactome in Resting Murine CD4 T Cells GSE18525: Identification of the Early VIP Transriptome and its Associated Interactome in Activated Murine CD4 T Cells Refer to individual Series
Project description:miRNA profiling of resting and activated T cells Two condition experiment, resting versus activated T cells, measured pooled samples from three independent stimulations
Project description:HIV-1 recurrently targets active genes that are positioned in the outer shell of the nucleus and integrates in the proximity of the nuclear pore compartment. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are proximal to super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location at the nuclear periphery during the activation of T cells. The clustering of these genes along with their transcriptional status are the major determinants of HIV-1 integration in T cells. Our results show for the first time the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.
Project description:Based on studies in knockout mice, several inhibitory factors such as TGF-beta, IL-10, or CTLA-4 have been implicated as gate keepers of adaptive immune responses. Lack of these inhibitory molecules leads to massive inflammatory responses mainly mediated by activated T cells. In humans, the integration of these inhibitory signals for keeping T cells at a resting state is less well understood. To elucidate this regulatory network we assessed early genome-wide transcriptional changes during serum deprivation in human mature CD4+ T cells. The most striking observation was a "TGF-beta loss signature" defined by downregulation of many known TGF-beta target genes. Moreover, numerous novel TGF-beta target genes were identified that are under the suppressive control of TGF-beta. Expression of these genes was upregulated once TGF-beta signaling was lost during serum deprivation and again suppressed upon TGF-beta reconstitution. Constitutive TGF-beta signaling was corroborated by demonstrating phosphorylated SMAD2/3 in resting human CD4+ T cells in situ, which were dephosphorylated during serum deprivation and re-phosphorylated by minute amounts of TGF-beta. Loss of TGF-beta signaling was particularly important for T cell proliferation induced by low-level T cell receptor and costimulatory signals. We suggest TGF-beta to be the most prominent factor actively keeping human CD4+ T cells at a resting state. Keywords: time course, dose response