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In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
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In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
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Modified Terminal Restriction Fragment Analysis for Quantifying Telomere Length Using In-gel Hybridization
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T cell memory revisited using single telomere length analysis.

Laureline Roger1, Kelly L Miners1, Louise Leonard1

  • 1Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, United Kingdom.

Frontiers in Immunology
|October 2, 2023
PubMed
Summary
This summary is machine-generated.

CD8+ memory T cell differentiation and replicative history are not directly linked. Telomere length analysis reveals distinct memory T cell subsets with varying telomere lengths, challenging linear differentiation models.

Keywords:
T cell differentiationT cell memoryT cell senescencereplicative historytelomere length (TL)

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Area of Science:

  • Immunology
  • Cellular Biology
  • T cell differentiation

Background:

  • The basis of long-lasting T cell memory is not fully understood.
  • The relationship between T cell phenotype, replication, and longevity is crucial for durable memory but difficult to study.
  • Conventional models propose a linear differentiation pathway for T cells.

Purpose of the Study:

  • To investigate the relationship between CD8+ memory T cell phenotype, replicative history, and longevity.
  • To elucidate the differentiation process of memory T cells using telomere length as a marker of replicative history.

Main Methods:

  • Phenotypically defined subsets of CD8+ memory T cells were isolated using markers like CD27 and CD45RA.
  • Telomere lengths were measured in these isolated subsets using single telomere length analysis (STELA).
  • Naive T cells were excluded based on CCR7 and CD45RA expression.

Main Results:

  • Subsets lacking CD45RA expression exhibited the shortest median telomere lengths.
  • Subsets expressing CD45RA showed the longest median telomere lengths.
  • CD27 expression correlated with longer telomere lengths, irrespective of CD45RA status.

Conclusions:

  • A disconnect exists between replicative history (inferred from telomere length) and CD8+ memory T cell differentiation.
  • The findings challenge the classical linear model of T cell differentiation.
  • Telomere length analysis provides insights into the heterogeneity and longevity of memory T cell subsets.