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IL-21/IL-15 regulation of CD8 T-cells

ABSTRACT: murine naive CD8+ T-cell samples for control or treated with 100ng/ml of IL-15 and/or IL-21 for 4 hours Keywords: other

ORGANISM(S): Mus musculus

PROVIDER: GSE2059 | GEO | 2004/12/11

SECONDARY ACCESSION(S): PRJNA91303

REPOSITORIES: GEO

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Transcription profiling of mouse na´ve CD8+ T-cells vs. control mouse total RNA treated with IL-15 and/or IL21 vs controls to investigate regulation of CD8 cells

Project description:murine naive CD8+ T-cell samples for control or treated with 100ng/ml of IL-15 and/or IL-21 for 4 hours

2007-11-23 | E-GEOD-2059 | biostudies-arrayexpress

Activation of Sez-4 cell line with IL-2, IL-15 or IL-21.

Project description:In this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells. Keywords: 3 replicates in each of 4 conditions

2008-02-19 | GSE8685 | GEO

Transcription profiling of human CD4+ cutaneous T-cell lymphoma (CTCL) Sez-4 cell line activated with IL-2, IL-15 or IL-21.

2008-04-09 | E-GEOD-8685 | biostudies-arrayexpress

Specific targeting of the common gamma chain blocks cooperative reprogramming of human tissue-resident cytotoxic T lymphocytes by IL-15 and IL-21

Project description:The common gamma chain (γc) is required for productive signaling by interleukin (IL)-15, IL-21 and IL-2, which are critically involved in immune activation and regulation. IL-21 and IL-15 are implicated in the pathogenesis of type-1 diabetes, graft-versus-host disease, and celiac disease (CeD), a gluten-mediated autoimmune-like enteropathy. Attempts to treat type-1 diabetes and graft-versus-host disease with biologics targeting one particular cytokine have failed. Both IL-15 and IL-21 have been suggested to drive activation of cytotoxic T cells (CTL) that are the effectors mediating tissue destruction in CeD and organ-specific autoimmune disorders. We show that the concomitant upregulation of IL-15 and IL-21 occurs only in full-blown CeD with villous atrophy. BNZ-2, a peptide that targets the γc, was able to block the cooperative IL-15/IL-21 mediated transcriptional activation of human tissue-resident intraepithelial CTL. Importantly, this inhibition was specific and did not interfere with IL-2 signaling, a cytokine with known immunoregulatory functions. Moreover, BNZ-2 blocked gluten-induced IFN-γ production in small intestinal organ cultures from CeD patients. These observations identify BNZ-2 as a therapeutic candidate for immune disorders in which IL-15 and IL-21 cooperate to induce CTL-mediated tissue damage.

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2021-10-06 | GSE185243 | GEO

Changes of gene expression patterns of mouse lung epithelial cells in response to IL-15 whether or not they have MCMV-memory CD8 T cells [mouse in vivo]

Project description:We report the differences of gene expression pattern of 4 different groups of mouse lung epithelial cells (Naive mouse without IL-15, Naive mouse with IL-15, MCMV-infected mouse without IL-15, and MCMV-infected mouse with IL-15). We found that mouse with MCMV-memory CD8 T cells response to IL-15 and the behaviors of cancer were changed compared to other groups.

2020-08-22 | GSE156605 | GEO

Cooperative armoring of CAR and TCR T-cells by T cell-restricted IL-15 and IL-21 universally enhances solid tumor efficacy

Project description:Chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapies are effective in a subset of patients with solid tumors, but new approaches are needed to enhance efficacy and universally improve patient outcomes. IL-15 and IL-21 are common cytokine-receptor gamma chain family members with distinct, pleiotropic effects on T-cells and other lymphocytes. We found that self-delivery of these cytokines by CAR or TCR T-cells prevents functional exhaustion by repeated stimulation and limits the emergence of dysfunctional natural killer (NK)-like T-cells. Across different preclinical murine solid tumor models, we observe enhanced regression with each individual cytokine but the greatest anti-tumor efficacy when T-cells are armored with both. Thus, the co-expression of membrane-tethered IL-15 and IL-21 represents a technology to enhance the resilience and function of engineered T-cells against solid tumors and could be applicable to multiple therapy platforms and diseases.

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Project description:The aim of this study was to compare the signaling cascades initiated by the two closely related cytokines IL-2 and IL-15. Considering the relevance of protein tyrosine phosphorylation in signal transduction, in order to quantify changes in protein phosphorylation in response to IL-2 and IL-15, we combined triple SILAClabeling of leukemic T-cells with phosphotyrosine (pY)-specific antibody-based protein enrichment followed by mass spectrometry (MS) analysis. Following the strategy described above, we managed to decipher in detail the complex signaling networks triggered by IL-2 and IL-15. Interestingly, a large number of components of the three main signaling pathways known to be initiated in response to the interleukins (JAK/STAT; RAS/MAPK; PI3K/AKT) were identified.

2014-09-23 | PXD001129 | Pride

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