scholarly journals Author response: Epigenetic modification of the PD-1 (Pdcd1) promoter in effector CD4+ T cells tolerized by peptide immunotherapy

2014 ◽  
Author(s):  
Rhoanne C McPherson ◽  
Joanne E Konkel ◽  
Catriona T Prendergast ◽  
John P Thomson ◽  
Raffaele Ottaviano ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Epigenetic Modification ◽  
Author Response ◽  
Peptide Immunotherapy

scholarly journals Author response: Distinct chromatin functional states correlate with HIV latency reactivation in infected primary CD4+ T cells

2018 ◽  
Author(s):  
Emilie Battivelli ◽  
Matthew S Dahabieh ◽  
Mohamed Abdel-Mohsen ◽  
J Peter Svensson ◽  
Israel Tojal Da Silva ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Author Response ◽  
Hiv Latency ◽  
Functional States

scholarly journals Progressive Immunodeficiency with Gradual Depletion of B and CD4+ T Cells in Immunodeficiency, Centromeric Instability and Facial Anomalies Syndrome 2 (ICF2)

Diseases ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 34 ◽  
Author(s):  
Georgios Sogkas ◽  
Natalia Dubrowinskaja ◽  
Anke K. Bergmann ◽  
Jana Lentes ◽  
Tim Ripperger ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Late Onset ◽  
Epigenetic Modification ◽  
Primary Immunodeficiency Disorder ◽  
Hematopoietic Stem ◽  
Facial Anomalies ◽  
Immunodeficiency Disorder ◽  
Centromeric Instability ◽  
Tract Infections

Immunodeficiency, centromeric instability and facial anomalies syndrome 2 (ICF2) is a rare autosomal recessive primary immunodeficiency disorder. So far, 27 patients have been reported. Here, we present three siblings with ICF2 due to a homozygous ZBTB24 gene mutation (c.1222 T>G, p. (Cys408Gly)). Immune deficiency in these patients ranged from late-onset combined immunodeficiency (CID) with severe respiratory tract infections and recurrent shingles to asymptomatic selective antibody deficiency. Evident clinical heterogeneity manifested despite a common genetic background, suggesting the pathogenic relevance of epigenetic modification. Immunological follow-up reveals a previously unidentified gradual depletion of B and CD4+ T cells in all three presented patients with transition of a common variable immunodeficiency (CVID)-like disease to late-onset-CID in one of them. Considering all previously published cases with ICF2, we identify inadequate antibody responses to vaccines and reduction in CD27+ memory B cells as prevalent immunological traits. High mortality among ICF2 patients (20%) together with the progressive course of immunodeficiency suggest that hematopoietic stem cell transplantation (HSCT) should be considered as a treatment option in due time.

scholarly journals Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells

Blood ◽  
2011 ◽  
Vol 117 (10) ◽  
pp. 2839-2846 ◽  
Author(s):  
Svenja Steinfelder ◽  
Stefan Floess ◽  
Dirk Engelbert ◽  
Barbara Haeringer ◽  
Udo Baron ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Transcriptional Activity ◽  
Epigenetic Modification ◽  
Cell Receptor ◽  
Noncoding Region ◽  
Differentially Methylated Region

Abstract CCR6 is a chemokine receptor expressed on Th17 cells and regulatory T cells that is induced by T-cell priming with certain cytokines, but how its expression and stability are regulated at the molecular level is largely unknown. Here, we identified and characterized a noncoding region of the human CCR6 locus that displayed unmethylated CpG motifs (differentially methylated region [DMR]) selectively in CCR6+ lymphocytes. CCR6 expression on circulating CD4+ T cells was stable on cytokine-induced proliferation but partially down-regulated on T-cell receptor stimulation. However, CCR6 down-regulation was mostly transient, and the DMR within the CCR6 locus remained demethylated. Notably, in vitro induction of CCR6 expression with cytokines in T-cell receptor-activated naive CD4+ T cells was not associated with a demethylated DMR and resulted in unstable CCR6 expression. Conversely, treatment with the DNA methylation inhibitor 5′-azacytidine induced demethylation of the DMR and led to increased and stable CCR6 expression. Finally, when cloned into a reporter gene plasmid, the DMR displayed transcriptional activity in memory T cells that was suppressed by DNA methylation. In summary, we have identified a noncoding region of the human CCR6 gene with methylation-sensitive transcriptional activity in CCR6+ T cells that controls stable CCR6 expression via epigenetic mechanisms.

scholarly journals Author response: Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells

2020 ◽  
Author(s):  
Isaac J Jensen ◽  
Samantha N Jensen ◽  
Frances V Sjaastad ◽  
Katherine N Gibson-Corley ◽  
Thamothrampillai Dileepan ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Author Response ◽  
Disease Development

scholarly journals Author response: Complement and CD4+ T cells drive context-specific corneal sensory neuropathy

2019 ◽  
Author(s):  
Derek J Royer ◽  
Jose Echegaray-Mendez ◽  
Liwen Lin ◽  
Grzegorz B Gmyrek ◽  
Rose Mathew ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Sensory Neuropathy ◽  
Author Response ◽  
Context Specific

scholarly journals Epigenetic modification of the PD-1 (Pdcd1) promoter in effector CD4+ T cells tolerized by peptide immunotherapy

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Rhoanne C McPherson ◽  
Joanne E Konkel ◽  
Catriona T Prendergast ◽  
John P Thomson ◽  
Raffaele Ottaviano ◽  
...  
Keyword(s):  
T Cells ◽  
Epigenetic Modification ◽  
Dna Hypomethylation ◽  
Peptide Immunotherapy ◽  
Tet Proteins ◽  
Genes Encoding ◽  
Inhibitory Molecule ◽  
Immune Pathology ◽  
Cell Expression ◽  
Cytosine Demethylation

Clinically effective antigen-based immunotherapy must silence antigen-experienced effector T cells (Teff) driving ongoing immune pathology. Using CD4+ autoimmune Teff cells, we demonstrate that peptide immunotherapy (PIT) is strictly dependent upon sustained T cell expression of the co-inhibitory molecule PD-1. We found high levels of 5-hydroxymethylcytosine (5hmC) at the PD-1 (Pdcd1) promoter of non-tolerant T cells. 5hmC was lost in response to PIT, with DNA hypomethylation of the promoter. We identified dynamic changes in expression of the genes encoding the Ten-Eleven-Translocation (TET) proteins that are associated with the oxidative conversion 5-methylcytosine and 5hmC, during cytosine demethylation. We describe a model whereby promoter demethylation requires the co-incident expression of permissive histone modifications at the Pdcd1 promoter together with TET availability. This combination was only seen in tolerant Teff cells following PIT, but not in Teff that transiently express PD-1. Epigenetic changes at the Pdcd1 locus therefore determine the tolerizing potential of TCR-ligation.

Author response for "Presence, function and regulation of IL‐17F‐expressing human CD4+ T cells"

2019 ◽  
Author(s):  
Lachrissa A. Burns ◽  
Ash Maroof ◽  
Diane Marshall ◽  
Kathryn J.A. Steel ◽  
Sylvine Lalnunhlimi ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Author Response

Author response for "Differentiation and activation of human CD4 T‐cells is associated with a gradual loss of myelin and lymphocyte protein"

2020 ◽  
Author(s):  
Judith Leitner ◽  
Kodchakorn Mahasongkram ◽  
Philipp Schatzlmaier ◽  
Karin Pfisterer ◽  
Vladimir Leksa ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Author Response ◽  
Gradual Loss
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