Unknown,Transcriptomics,Genomics,Proteomics

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Changes in gene expression analysis of alphaCD3alpha/CD28 activated human naive and memory regulatory T cells (Treg) upon IL-7 treatment as measured by quantitative PCR array

ABSTRACT: This study evaluated changes in gene expression upon IL-7 treatment in human naive and memory Treg. CD4+CD25+CD127low naïve and memory Treg were isolated from fresh PBMC and separately stimulated with ?CD3?/CD28 coupled beads (Invitrogen-Dynal) at a 1:10 bead/T cell ratio, treated with or without 10 ng/ml of rhIL-7 (R&D Systems) for 16 hours. qPCR gene expression profiling of CD4+CD25+CD127low naïve and memory Treg obtained from 2 separate donors. Cell lysates were prepared separately from the 2 donors and pooled prior to RNA extraction.

ORGANISM(S): Homo sapiens

SUBMITTER: Anke Theil

PROVIDER: E-GEOD-40755 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

IL-7 abrogates suppressive activity of human CD4+CD25+FOXP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells.

Heninger Anne-Kristin AK Theil Anke A Wilhelm Carmen C Petzold Cathleen C Huebel Nicole N Kretschmer Karsten K Bonifacio Ezio E Monti Paolo P

Journal of immunology (Baltimore, Md. : 1950) 20121105 12

CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) control the activation and expansion of alloreactive and autoreactive T cell clones. Because uncontrolled activation and expansion of autoreactive T cells occur in an IL-7-rich environment, we explored the possibility that IL-7 may affect the function of Treg. We show that the functional high-affinity IL-7R is expressed on both naive and memory Tregs, and exposure to IL-7 results in STAT-5 phosphorylation. Naive, but not memory, Tregs proliferated ...[more]

PMID: 23129754

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Project description:We investigated the roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus (DENV). Double-deficient Irf-3-/-7-/- mice infected with the DENV2 strain S221 possessed 1,000-150,000 fold higher levels of viral RNA than wild-type and single-deficient mice 24 hours after infection; however, they remained resistant to lethal infection. IFN-α/β was induced similarly in wild-type and Irf-3-/- mice post DENV infection, whereas in the Irf-7-/- and Irf-3-/-7-/- mice, significantly low levels of IFN-α/β expression was observed within 24 hours post-infection. IFN-stimulated gene (ISG) induction was also delayed in Irf-3-/-7-/- mice relative to wild-type and single-deficient mice. In particular, Cxcl10 and Ifnα2 were rapidly induced independently of both IRF-3 and IRF-7 in the Irf-3-/-7-/- mice with DENV infection. Higher levels of serum IFN-γ, IL-6, CXCL10, IL-8, IL-12 p70, and TNF were also observed in Irf-3-/-7-/- mice 24 hours after infection, at which time point viral titers peaked and started to be cleared. Antibody-mediated blockade experiments revealed that IFN-γ, CXCL10, and CXCR3 function to restrict DENV replication in Irf-3-/-7-/- mice. Additionally, the ISGs Cxcl10, Ifit1, Ifit3, and Mx2 can be induced via an IRF-3- and IRF-7-independent pathway that does not involve IFN-γ signaling for protection against DENV. Collectively, these results demonstrate that IRF-3 and IRF-7 are redundant, albeit IRF-7 plays a more important role than IRF-3 in inducing the initial IFN-α/β response; only the combined actions of IRF-3 and IRF-7 are necessary for efficient control of early DENV infection; and the late, IRF-3- and IRF-7-independent pathway contributes to anti-DENV immunity. To identify the antiviral genes that are controlled by IRF-3 and IRF-7 signaling during DENV infection, we examined a panel of ISG expression in the spleens of wild-type, Irf-3-/-, Irf-7-/- and Irf-3-/-7-/- mice at 12 or 24 hours after DENV infection using a quantitative PCR array kit. The fold changes in expression of 55 genes from infected mice were normalized to that of strain-matched naïve mice.

Dataset Information

Changes in gene expression analysis of alphaCD3alpha/CD28 activated human naive and memory regulatory T cells (Treg) upon IL-7 treatment as measured by quantitative PCR array

Publications

IL-7 abrogates suppressive activity of human CD4+CD25+FOXP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells.

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