Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse resting and activated CD8+ T cells

ABSTRACT: This experiment compared the expression of mRNAs and noncoding RNAs between resting and activated CD8+ effector T cells, with the primary aim of identifying noncoding RNAs that were dynamically regulated during T cell activation.

ORGANISM(S): Mus musculus

SUBMITTER: Marcel Dinger

PROVIDER: E-TABM-491 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-wide identification of long noncoding RNAs in CD8+ T cells.

Pang Ken C KC Dinger Marcel E ME Mercer Tim R TR Malquori Lorenzo L Grimmond Sean M SM Chen Weisan W Mattick John S JS

Journal of immunology (Baltimore, Md. : 1950) 20090601 12

Previous research into the molecular mechanisms that underlie Ag-specific CD8(+) T cell differentiation and function has largely focused on the role of proteins. However, it is now apparent that the mammalian genome expresses large numbers of long (>200 nt) nonprotein-coding RNAs (ncRNAs), and there is increasing evidence that these RNAs have important regulatory functions, particularly in the regulation of epigenetic processes underpinning cell differentiation. In this study, we show that CD8(+ ...[more]

PMID: 19494298

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Project description:The activation of TLR-MyD88 (Toll like receptor- Myeloid differentiation factor 88) signaling within T cells functions as a potent costimulatory signal that boosts antitumor and antiviral responses. However, the molecular mechanisms underlying the costimulatory processes are poorly understood. We compared microarray gene analysis data between TLR1-TLR2 stimulated and unstimulated T cell receptor transgenic âpmelâ and MyD88-/-pmel CD8+ T cells and identified changes in the expression levels of several TNF family members. In particular, TLR-stimulation increased 4-1BB levels in pmel but not in MyD88-/-pmel T cells. A link between 4-1BB and TLR1-TLR2 signaling in CD8+ T cells was highlighted by in fact that 4-1BB-/- T cells exhibited suboptimal responses to TLR1-TLR2 agonist, but responded normally to CD28 or OX40 costimulation. Moreover, blocking 4-1BB signaling with antibodies also hindered the costimulatory effects of the TLR1-TLR2 agonist. The elevated levels of 4-1BB transcripts in TLR1-TLR2âstimulated cells were not due to increased mRNA stability nor increased histone activation but instead were associated with increased binding of p65 and c-Jun to two distinct 4-1BB promoter sites. Combining TLR1-TLR2 ligand with an agonistic anti-4-1BB antibody enhanced the antitumor activity in mice with established melanoma tumors. These studies reveal that the costimulatory effects of TLR1-TLR2 signaling in CD8+ T cells are in part mediated by 4-1BB and are important for mounting an effective antitumor immune response. CD8+ T cells from the B6.Cg-Thy1/Cy Tg(TcraTcrb)8Rest/J mice, referred to as âpmelâ T cells or from MyD88 knockout pmel mice (MyD88â/âpmel) were sorted. pmel and MyD88â/âpmel T cells were activated using MyD88â/â CD8 T cell-depleted splenocytes pulsed with 10ng/ml of mgp100. This was with or without 10Âµg/ml of Pam3CSK4. pmel or MyD88â/âpmel CD8 T cells were enriched and used for the extraction of RNA used for genomic analysis.

Dataset Information

Transcription profiling of mouse resting and activated CD8+ T cells

Publications

Genome-wide identification of long noncoding RNAs in CD8+ T cells.

Similar Datasets

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