Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse IL-7Rhi/lo effector CD8 T cells on day 6/7 after LCMV armstrong infection

ABSTRACT: At the peak of the CD8 T cell response to acture viral and bacterial infections, expression of the Interleukin-7 Receptor (IL-7R) marks Memory Precursor Effector CD8 T Cells (MPECs) from other Short-Lived Effector CD8 T cells (SLECs), which are IL-7Rlo. This study was designed to determine the gene expression differences between these two subsets of effector CD8 T cells. Experiment Overall Design: This study compared IL-7Rhi and IL-7Rlo LCMV-specific P14 Transgenic CD8 T cells, sorted from LCMV armstrong infected recipient mice 6/7 days after infection. Data includes 3 independent replicates for the IL-7Rhi and IL-7Rlo groups.

ORGANISM(S): Mus musculus

SUBMITTER: Susan Kaech

PROVIDER: E-GEOD-8678 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Using killer cell lectin-like receptor G1 as a marker to distinguish terminal effector cells from memory precursors, we found that despite their diverse cell fates both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making IL-2 thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid re-call responses. Mechanistic studies showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation towards the tail-end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation Experiment Overall Design: An important question in memory development is understanding the differences between effector CD8 T cells that die versus effector cells that survive and give rise to memory cells. In this study we provide a comprehensive phenotypic, functional and genomic profiling of terminal effectors and memory precursors, towards better understanding the generation of these subsets. The two effector subsets were FACS purified during the early expansion phase (Days 4-5 post-infection) and extensively analyzed for their phenotypic (eg. CD127, CD62L, CD27, Bcl-2, Granzyme B, etc.) and functional properties (cytokine production, cytotoxicity, homeostatic proliferation, recall proliferation), and gene expression profiles (by genome-wide microarray analyses). Mechanistic studies involving the extent of proliferation and duration of antigen stimulation on memory differentiation potential of effectors were also performed using adoptive transfer techniques.

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Transcription profiling of mouse IL-7Rhi/lo effector CD8 T cells on day 6/7 after LCMV armstrong infection

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