On triggering of the T cell receptor CD8 T lymphocytes downregulate expression of the transcription factor KLF2. KLF2 expression remains low as these cells differentiate to Cytotoxic T lymphocytes (CTL) but may be re-expressed depending on the local environmental signals.
The impact of KLF2 modulation on the transcriptional program and function of CD8 T cells.
Specimen part
View SamplesThe present study reports an unbiased analysis of the cytotoxic T cell serine-threonine phosphoproteome using high resolution mass spectrometry. Approximately 2,000 phosphorylations were identified in CTLs of which approximately 450 were controlled by TCR signaling. A significantly overrepresented group of molecules identified in the phosphoproteomic screen were transcription activators, co-repressors and chromatin regulators. A focus on the chromatin regulators revealed that CTLs have high expression of the histone deacetylase HDAC7 but continually phosphorylate and export this transcriptional repressor from the nucleus. HDAC7 dephosphorylation results in its nuclear accumulation and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. The screening of the CTL phosphoproteome thus reveals intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators in CTLs and determine the CTL functional program. We used Affymetrix microarray analysis to explore the molecular basis for the role of HDAC7 in CTLs and the impact of GFP-HDAC7 phosphorylation deficient mutant expression on the CTL transcriptional profile.
Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes.
Specimen part
View SamplesComparison of transcriptional profile of TCR stimulated P14-TCR wild-type and P14-PKD2 null murine lymph node cells
Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells.
Specimen part
View SamplesIn cytotoxic T cells (CTL), Protein Kinase B /Akt is activated by the T cell antigen receptor (TCR) and the cytokine Interleukin 2 (IL2), in part by phosophorylation of Akt by Phospholipid dependent kinase 1 (PDK1).
Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism.
Specimen part
View SamplesComparison of transcriptional profile of CD8 cytotoxic T lymphocytes terated with the mTORC1 inhibitor rapamycin or the mTOR inhibitor KU-0063794 and comparison with proteomic analysis.
The cytotoxic T cell proteome and its shaping by the kinase mTOR.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesWe screened SLE monocytes from 19 SLE patients and selected 4 that induced CD4+ T cell proliferation in vitro and 4 that did not. CFSE labeled CD4-T cells (105) were incubated with SLE monocytes (2 x 104). Cells were harvested at 6 hours for RNA extraction.
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesTo explore the full extent of IFN-regulated transcriptional changes, we exposed monocytes from two healthy donors to recombinant type I IFN (IFN-2b) in vitro. RNA was extracted at different incubation times (1, 6, 24, 48 and 72 hrs) and the expression data was normalized to that of monocytes cultured with medium.
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Specimen part, Disease, Disease stage, Treatment, Time
View SamplesTo directly compare the SLE monocyte transcriptional program with that of blood mDC precursors, we purified lineage HLA-DRhighCD11chigh mDCs and CD14+ monocytes from the blood of five healthy donors. Their gene expression profiles were then compared to those of blood SLE monocytes. An unsupervised clustering analysis of transcripts present in >20% of the samples classified healthy monocytes, SLE monocytes and healthy mDCs into three well defined groups. A supervised analysis was then performed to find genes: 1) differentially expressed in healthy mDCs compared to monocytes; 2) shared by healthy blood mDCs and SLE blood monocytes.
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Specimen part, Disease, Disease stage, Subject
View SamplesTo better characterize the molecules that could potentially confer antigen presenting capacity to SLE monocytes, we assessed their gene expression profile.
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Specimen part, Disease, Disease stage, Subject
View Samples