Epigenetic modification of the PD-1 (Pdcd1) promoter in effector CD4(+) T cells tolerized by peptide immunotherapy
ELIFE
Authors: McPherson, Rhoanne C.; Konkel, Joanne E.; Prendergast, Catriona T.; Thomson, John P.; Ottaviano, Raffaele; Leech, Melanie D.; Kay, Oliver; Zandee, Stephanie E. J.; Sweenie, Claire H.; Wraith, David C.; Meehan, Richard R.; Drake, Amanda J.; Anderton, Stephen M.
Abstract
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 PD1. Epigenetic changes at the Pdcd1 locus therefore determine the tolerizing potential of TCR-ligation.
Polymorphisms in PDCD1 gene are not associated with aplastic anemia in Chinese Han population
RHEUMATOLOGY INTERNATIONAL
Authors: Ming, Z. J.; Hui, H.; Miao, M.; Qiu, Y. H.; Zhang, X. G.
Abstract
Programmed cell death 1 (PD-1) has recently been reported to have a genetic association in several autoimmune diseases. The object of this study was to investigate the association of PD-1 polymorphisms with aplastic anemia (AA) in the Chinese Han population. In a case-control association study, three single-nucleotide polymorphisms (SNP), PD-1.3 G/A, PD-1.5 C/T, and PD-1.9 T/C, were genotyped in 166 AA patients and 264 healthy controls using polymerase chain reaction-restriction fragment length polymorphism assay. All genotype distributions in the patients and the controls were in Hardy-Weinberg equilibrium. The associations of genotypes and alleles with AA were analyzed. No differences in genotype and allele frequencies were elucidated for SNPs in intron 4 and exon 5. In conclusion, we show no association of selected SNPs in PDCD1 gene with AA in the Chinese Han population.
COA
Publication 
Loading ......
