Dataset Information

The Maintenance of Telomere Length in CD28+ T Cells During T Lymphocyte Stimulation.

ABSTRACT: Telomerase activity is not readily detected in resting human T lymphocytes, however upon antigen presentation, telomerase is transiently upregulated. Presently, it is not known if telomerase activation is necessary for the proliferation of T cells or for the maintenance of telomere lengths. In this study, we found that telomerase activation is not required for the short- term proliferation of T cells and that telomeres progressively shorten in a heterogeneous population of T cells, even if telomerase is detected. By measuring telomerase activity at the single-cell level using quantitative ddPCR techniques (ddTRAP) and by monitoring changes in the shortest telomeres with more sensitive telomere length measurement assays, we show that only a subset of CD28+ T-cells have robust telomerase activity upon stimulation and are capable of maintaining their telomere lengths during induced proliferation. The study of this T-cell subset may lead to a better understanding on how telomerase is regulated and functions in immune cells.

SUBMITTER: Huang EE

PROVIDER: S-EPMC5533788 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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The Maintenance of Telomere Length in CD28+ T Cells During T Lymphocyte Stimulation.

Huang Ejun Elijah EE Tedone Enzo E O'Hara Ryan R Cornelius Crystal C Lai Tsung-Po TP Ludlow Andrew A Wright Woodring E WE Shay Jerry W JW

Scientific reports 20170728 1

Telomerase activity is not readily detected in resting human T lymphocytes, however upon antigen presentation, telomerase is transiently upregulated. Presently, it is not known if telomerase activation is necessary for the proliferation of T cells or for the maintenance of telomere lengths. In this study, we found that telomerase activation is not required for the short- term proliferation of T cells and that telomeres progressively shorten in a heterogeneous population of T cells, even if telom ...[more]

PMID: 28754961

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Project description:BackgroundTelomeres at the ends of eukaryotic chromosomes play a critical role in maintaining the integrity and stability of the genome and participate in the initiation of DNA damage/repair responses.MethodsWe performed a case-control study to evaluate the role of three SNPs (TERT-07, TERT-54 and POT1-03) in telomere maintenance genes previously found to be significantly associated with breast cancer risk. We used sister-sets obtained from the New York site of the Breast Cancer Family Registry (BCFR). Among the 313 sister-sets, there were 333 breast cancer cases and 409 unaffected sisters who were evaluated in the current study. We separately applied conditional logistic regression and generalized estimating equations (GEE) models to evaluate associations between the three SNPs and breast cancer risk within sister-sets. We examined the associations between genotype, covariates and telomere length among unaffected sisters using a GEE model.ResultsWe found no significant associations between the three SNPs in telomere maintenance genes and breast cancer risk by both conditional logistic regression and GEE models, nor were these SNPs significantly related to telomere length. Among unaffected sisters, shortened telomeres were statistically significantly correlated with never hormone replacement therapy (HRT) use. Increased duration of HRT use was significantly associated with reduced telomere length. The means of telomere length were 0.77 (SD = 0.35) for never HRT use, 0.67 (SD = 0.29) for HRT use < 5 yrs and 0.59 (SD = 0.24) for HRT use ≥ 5 yrs after adjusting for age of blood donation and race and ethnicity.ConclusionsWe found that exogenous hormonal exposure was inversely associated with telomere length. No significant associations between genetic variants and telomere length or breast cancer risk were observed. These findings provide initial evidence to understand hormonal exposure in the regulation of telomere length and breast cancer risk but need replication in prospective studies.

Dataset Information

The Maintenance of Telomere Length in CD28+ T Cells During T Lymphocyte Stimulation.

Publications

The Maintenance of Telomere Length in CD28+ T Cells During T Lymphocyte Stimulation.

Similar Datasets

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